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Current RNA vaccines protect against worrying coronavirus variants (nature.com)
330 points by gmays on May 11, 2021 | hide | past | favorite | 304 comments



I literally saw the opposite headline about Pzifer versus a strain in India today

The actual article said "modest antibody evading capabilities“

I hate that the internet has become this way


"modest antibody evading capabilities“

This generally means that a pseudovirus built with the mutated spike escapes some monoclonal antibodies and has reduced neutralization titers against convalescent sera, which is fairly normal and doesn't add up to an escape mutation.

When it mutates enough to form an actual escape mutation that will probably come at a cost to the virus for transmissibility/virulence/viral load because it will need to escape at ~20 different epitopes. And still cross reactive T-cells will likely identify the new strain enough and active your immune system to contain it so that it acts more like a common cold than COVID-19.

Booster shots are probably still not a bad idea though, the more it gets boxed in by our immune systems, the more it'll have to make those costly evolutionary choices and become less virulent.


In a r/askscience , there was a report that they are also working on a surface identifying vaccine, which doesn’t mutate (as much?), instead based on the spike protein. They didn’t earlier because it takes a longer time to develop and is harder.


vaccines don't "mutate" ?? Are you saying they're developing more broadband vaccine that can handle more mutation by the virus?


Not OP, but I think what was meant is identifying a vaccine that targets proteins(s) on the surface of the virus rather than only the little "spikes" that protrude from it. Early vaccine development latched onto the idea that the spike proteins are critical to the virus' ability to infect humans, so mutations would likely/hopefully/maybe make the virus less dangerous to humans anyway.

But, it would be ideal if we could also find proteins on the surface of virus that are less likely to mutate (than other proteins in the virus) that we could teach our immune systems to look for.


It sounds like you might be a good person to review and give your thoughts on this interview between Bret Weinstein, an evolutionary biologist, and Geert Vanden Bossche, a virologist, who discuss this in length and detail it for layperson? https://www.youtube.com/watch?v=BNyAovuUxro


Skimmed it, seems like its a lot of bullshit wrapped up in plausible sounding science.

The H1N1 pandemic is an interesting historical model, and the more deadly later waves indicate that more virulent variants were produced in that pandemic as well. He seems to be arguing that vaccines are causing the variants and that natural herd immunity is better, which is bullshit.

First of all the vaccines are 80-90% effective, even against variants, which greatly reduces the number of people that the vaccine can use to mutate new variants. When there are vaccination failures the vaccines prevent symptoms, prevent viral load and shedding and transmissibility. That cuts down on the production of variants as well.

There's also considerable cross protection in the human immune system since immunity isn't binary like an on/off switch. As a historical example the people born before 1957 were exposed to H1N1 and had cross reactive T-cells to the 2009 H1N1 pandemic. So after mutating in pigs for 50 years the human immune system still recognized the H1 envelope protein sufficiently to take the edge off of that pandemic to make it essentially nothing. And we vaccinated younger people (with I.M. flu vaccines) and didn't see the emergence of hugely virulent H1N1 variants.

The variants are arising now because there's a decreasing fraction of the population which is 100% susceptible to infection and the virus is chasing after that decreasing fraction by increasing transmissibility, viral load and virulence. The vaccines will be effective at taking people out of that 100% susceptible pool even though they're not absolutely perfect. The virus will eventually run out of that 100% susceptible pool and will have to start optimizing for costly immune escape variants which will lower its virulence in order to try to get around vaccinated and recovered individuals immune systems.

This right now, with the evolution of more virulent variants is the WORST time to be playing the natural herd immunity card. Everyone needs to get vaccinated to protect themselves and to put the virus under more pressure to make costlier mutations than it has been able to make so far. Spreading this idea that the vaccines are producing the more lethal variants is literally going to get people killed by having them skip vaccinations and wind up contracting one of the most lethal variants the pandemic is likely to produce. That is optimizing for the worst possible roll of the dice for yourself.

So yeah, he should be banned off of social media and you're killing people by spreading this misinformation.

Cheers.


The COVID-19 vaccine is less effective against the variants, and arguably unknown if immunity developed from dead-virus based vaccines would provide higher effectiveness against variants and reduce potential for escape.

You're arguing to ban critical thinkers having a conversation, perhaps instead you should be ban off social media for wanting to censor intellectuals/critical thinkers?

Especially since you're seemingly giving a well-thought out response but you immediately admit you skimmed it, and then wrongly claim they're pushing for herd immunity.

You also reference cross immunity, however those weren't using mRNA vaccines afaik, and so the mechanism and spread that the immunity will cover for variants won't be the same.

I was wrong, you're not as rational or thorough of a person I thought you might be based on your initial explanation that I responded to.


If mutations are random events, how does a virus know it is under more pressure because randomizing events occur less often?


> the more it'll have to make those costly evolutionary choices and become less virulent

Why would evolution select for less virulence in a virus like this? Given covid doesn't rely on symptoms to spread like the common cold seems to, it would seem like the evolutionary pressure would be the opposite. Rather than moderate symptoms, instead jack up viral loads in the host as quickly as possible to spread before the immune system gets involved.

/not a biologist


That is what it is doing right now.

But it is doing that in response to evolutionary pressure because when a good fraction of the people are recovered or vaccinated then an R0 of 3.0 doesn't work as well when its chasing after those remaining susceptible people.

There'll be an upper limit to how much it can increase its binding to ACE / viral load / R0 though. Once you hit that point infections should fall off a cliff. Then the virus will start to come under pressure to achieve immune escape.

To really achieve immune escape the virus should have to make costly mutations. It shouldn't be able to pick the most optimized spike conformation, it'll have to pick a spike conformation that immune systems don't recognize.

It can't be ruled out that the virus has so much "room" to mutate on the spike protein that high virulence total escape mutants could be formed, but probably not. There are estimated to be 20 epitopes on the spike that the immune system recognizes and to really escape it needs to mutate sufficient to change all of them. Some of them are likely to be expensive to the virus. And if we get booster shots like I said to box it in more, then it should run out of room and start to mutate more towards stealth and less towards virulence.

And there's historical parallels to 1918. At first the H1N1 virus came back in waves that became more virulent. Then once more than half the world had been infected it started to come back as seasonal influenza and spread endemically in humans until 1957. Some of that is likely partial immunity from previously infected individuals, some of that is probably that the virus stated to favor evolving to escape detection and not for virulence and transmissibility.


There's physical limitations on what it can do, basically.

Every mutation runs the risk of reducing its binding affinity to ACE receptors to get inside cells - or might impede cell entry functions.

Given the amount of infection out there, whatever "easy" mutations might've been available to it clearly haven't been very useful in increasing its rate of spread - and haven't touched anything the vaccines target.

So it's quite likely that whatever needs to happen to evade the vaccines is otherwise deleterious to its virulence.


I’m curious, what is your education background in?

Do you have some sort of medical education or this is a regurgitation of some sources you’ve read as a hobbyist?

I ask this because you seem to talk from a place of authority and fact and i respect that but typically thought of Ycomb as a place comp sci folks usually congregate.


Maybe you should ask for sources instead. Authority is the wrong thing to trust in science


However, isn't this how Bayesian thinking works? You give a higher prior to your believe depending of the source.


That's why we ask for sources. If one doesn't trust lamontcg to know what they're talking about, we shouldn't trust them to be honest about that fact. We're often more likely to have Bayesian priors about a primary source than the people who refer to them.


Yes, but in this case authority would be your prior, and a source would be the data to update that prior. If you are only relying on authority, you are solely going off of your personal biases, which while potentially informative, isn't as useful as actual data.


A perfectly reasonable approach; but then it is easier to ask people you trust rather than reading HN. Anonymous internet people are inherently unreliable.


Authority is constantly used as an effective source of trust in science.


As an effective shortcut but it's still the wrong thing, ultimately, to trust.


A scientist who doesn’t use sources effectively and accurately themselves is not to be trusted as either an authority or as a scientist. It is the greatest sin for a researcher.


What is the alternative? Everyone grabs postdoctorate degrees in everything that might come up?


Your question shows why it is a shortcut.


Heuristic might be a better term.


There is also a massive reproducibility crisis in science, and the two points are not not unrelated.


The “reproducibility crisis” is largely overblown. Individual scientific papers have always been close to junk on average. Look at a wide swath of papers from say the 1950’s or even 1850’s and you see not just poor methods but also outright fraud.


It absolutely isn't overblown, and "individual scientific papers have always been close to junk on average" is a pretty damning indictment.

Meta-studies have found that, depending on the field, up to 70% of published papers can't be reproduced. I'm not sure its possible for considering that a crisis to ever be "overblown".


Even 30% of papers being reproducible is orders of magnitude better than random chance. That’s the signal that pushes science forward.

As to old papers, go back to the 1950’s and plate tectonics was still being debated. What do you think the other geological papers where based on? When you read a specific older paper it’s generally because it stood the test fo time, but that’s just selection bias.


I completely agree... in principle. That being said, I actually think we tend to underestimate the value of trusting experts. Often times the sources out there that one could be quoting espouse conflicting and ambiguous conclusions and it ironically takes an expert to be able to parse through them all. If we could all trust experts a bit more and, rather than ask for sources, instead ask our experts to explain their reasoning to us, I think we'd all be better off in the long run in that we'd actually be learning from them rather than trying to constantly bootstrap becoming experts ourselves.


Unless you have a background in immunology the sources are probably not terrible useful to you.


Probably, but not definitely. The only thing preventing you from understanding the sources yourself is some effort. It's not as hard as it is sometimes imagined.


One problem with that is that any individual study should be read in the context of other published literature, if you want to form an informed opinion. The only alternative is authority - either looking at the journal where it was published, the authority of the authors, or the authority of someone who recommended the paper.

Otherwise, it's easy to find plausible-sounding papers that have failed to reproduce in subsequent studies, that use too low samples compared to similar studies with different conclusions, that were later retracted etc.


Oh, they will be, but in the opposite way to what GP seems to want. That is, I'd look at the sources as further sources of authority :). E.g. a bunch of papers from multiple teams, with some published by high-profile journals or authored by well-known researchers, indicates it's relatively safe to trust their conclusions. A bunch of papers from the same few people who seem to want to push their pet theory indicates low trustworthiness and need for independent verification.

Unless you've studied the domain in question in depth, it's not like you could use the citations in any other way. Trust, as a heuristic, is fundamental to advanced research as much as it is for everything else in society.


They could be useful to somebody else, and that's a good enough reason to have them.


I've been reading HN for over a decade and I've seen comments from people with a huge variety of backgrounds. Many people switch fields later in life or they might just be interested in technology/startups.


> or this is a regurgitation of some sources you’ve read as a hobbyist

I'm sure it's not your intention, but this phrase might be mistaken for an offensive, negative critique of the OP's abilities, which may make the OP hesitate to respond, or respond defensively.

If you are purely seeking information, without prejudice, then your question would be more effective if you ended it before the 'or'.


I’ve no knowledge regarding that commenter, but there are large amounts of diverse experts in various fields on here. It’s one of the reasons I like it so much here


>but there are large amounts of diverse experts in various fields on here.

Yeah, and they mostly keep their mouths shut except to confirm what everyone is already saying because trying to correct the narrative or dispel a popularly held belief on a site with a voting mechanism is an exercise in futility. Nobody will read your comment when it's dead so why bother.


I'm sure plenty of people here enable showdead. I do at least.


HN has tons of users with training in bio and medicine, including a surprising number of practicing physicians and academics. This is a big community. People's mental image of it tends to be much smaller and less diverse than it actually is. It's a lot more than "comp sci" folks, which is good, because it's not supposed to be limited that way.


I can't answer to the specific source you saw but you are most likely misinterpreting the concepts at play.

When you see articles about antibody evading or antibody escape the research is not dealing in absolutes. It's perfectly possible for there be some antibody escape but the overall immune response is perfectly adequate to quickly deal with an infection.

With the variants of concern so far we've seen a similar pattern, sometimes there can be a reduction in efficacy of the vaccines (remember all efficacy endpoints are measured against preventing symptomatic disease), but at the same time they mostly provide a very high protection against severe disease and hospitalization.

So the two headlines are both perfectly correct, the current variants of concern have the ability to demonstrate antibody escape at a slightly higher rate than the original variant, but the current vaccines still protect people against sever disease.


Usually its because they aren't always talking about the exact same thing. So far at least, whenever you see a headline about a strain "evading antibody capabilities", it means that they've found that the strain induces a lower reading on various measures of immunity in sera, like neutralizing titers, than previous strains do.

However, a measure of immunity like neutralizing titers isn't a 1:1 function of immunity.

So a simple example (with made up numbers) would be that a particular strain sees a 6x reduction in neutralizing titers compared to the original strain, but it doesn't mean much because there are enough neutralizing titers provided by the vaccine that even a 15x fold reduction would provide strong protection. In this case you could say that the strain has modest antibody evading capabilities AND that the vaccine provides strong protection against it.

I think most media outlets tend to overemphasize the "evasion" angle in headlines, either due to incompetence or for clickbait purposes. Given that almost every single one I've read has a quote from a physician along the lines of "This isn't anything to worry about, it still provides protection" buried a few paragraphs down, I'm assuming its the latter.


This article doesn't seem to address any of the strains originating in India, fwiw. My guess is that they haven't known of them long enough to understand their reaction in vaccinated people.


The popular media has done a huge disservice by naming this the "Indian double mutant." It's two changes that have been seen in other variants and have been studied already.

The "double mutation" is L452R and E484Q. L452R is the defining feature of the B.1.429 variant (California). E484Q has been seen in derivatives of B.1.429 and in bunches of other variants in the US. It has some antibody evasive properties, but not enough to render vaccines ineffective. Yes, the E484K mutation seen in B.1.351, P.1, and P.2 has been more studied, but E484Q has been studied too.

Double mutant makes it sound like it is something entirely novel that is going to murder us all.


Isn't the fact that those two mutations pop up in Brazil, South Africa and now India a good thing?

That could mean it's likely the virus is running out of useful mutations?


Yes. I've heard this argument being made by Christian Drosten (a German virologist specializing in coronaviruses) in his podcast a few months back.


I assumed that the common mutations were the result of travel. Is that not the case? Is the belief that the virus is hitting the same mutations independently in multiple places?


While its possible some of it is due to travel, I've definitely read that there is plenty of reason to believe these mutations are arising independently in different nations. Basically the virus is mutating all the time, but the vast majority of mutations are meaningless or have negative impact on the fitness of the virus. However some mutations may be more commonly observed, either because certain mutations in particular regions are more common (due to the physics/chemistry of the proteins involved) or because the mutation changes the virus in a way that makes it more like to stick and ultimately spread among the population. Some of these mutations are basically like local minimums in a mathematical function, and its not uncommon to see random traversals of that function coalesce around these minimums, at least temporarily.


> this the "Indian double mutant."

I've actually seen it referenced as the "triple mutant"!


India is by and large not using Pfizer. Evidence to date points to AstraZeneca (which they are using) being quite effective in preventing serious illness.


So far ALL vaccines are effective against serious illness with all variants.


This has me wondering: Are there any events in history (with any other viruses) where this hasn't proven to be the case?

Viruses that we've developed vaccines for, that have eventually been rendered inneffective due to a mutation? Is it a common occurence?


Not rendered ineffective per se, but it's part of why you need a flu shot every year. There are a lot of strains and they mutate a lot, so we do a best guess of which current strains will be the most infectious in a given year and develop vaccines targeting those strains.

Generally the vaccines are moderately effective, but it's because we update them every year. If we didn't, they wouldn't be.

That being said there are efforts underway to make vaccines that would be more broadly effective against the flu and will be less susceptible to variants escaping ("universal flu vaccines"), and so this may not always be true in the future.

In the meantime, mRNA vaccines will likely be a huge aid for fighting the flu, because they can be manufactured rapidly for specific strains. Currently there's a six-month or longer lead time for inactivated- or attenuated-virus vaccines — which is what flu shots generally are — and sometimes new variants pop up or are discovered to be more infectious in between the manufacturing start date and that year's flu season.

Moderna apparently plans to make COVID booster shots that are also flu shots, although they may not be ready this year.


>but it's because we update them every year.

OK, this is the part I wasn't aware of. I assumed (dangerous, I know) that each year's 'new' flu vaccine was really just a new 'blend' of existing proven vaccines, for the most prevalent strains that year.

Edited to remove badly conceived question. New Question: How often do we have to develop novel vaccines for new Flu variants?


From this [1] Wikipedia article it looks like there aren't new strains every year, but generally every few years there will be a new variant that replaces an older variant in the mix. The oldest variant currently in flu vaccines is from 2013, and the newest is from 2019.

That being said, the process generally doesn't change — you still grow and kill (or grow and weaken) viruses the same way, you just start from a different base strain. For already-approved inactivated-virus flu vaccines, the FDA does not require new clinical trials for strain updates, and for already-approved attenuated virus vaccines, they only require very minimal trials (300 adults to prove adequate attenuation) [2]. So they're not novel in the sense of the COVID vaccines, which needed large scale clinical trials to prove efficacy — the flu vaccines have generally already proved efficacy, so for strain updates the most they need to prove is safety.

1: https://en.m.wikipedia.org/wiki/Influenza_vaccine

2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947948/


Thanks for this


yes - they make a prediction about which strains will be prevalent every Northern and Southern winters - it's a bit of a crap shoot, they're not always right though usually they are.

As I understand it predicting which flu strains to vaccinate this year is particularly hard because mask wearing/isolation/social distancing has reduced flu levels enough that they don't have a lot of data to base their predictions on


It seems like the flu virus is the example you want right? Every year the vaccines delivered is a cocktail based on the predicted most common variants, because no one vaccine can protect against them all.


I considered that, but as I understand it (this could wrong) the variants that are more prevalent each year are pre-existing and we just don't know which ones will be 'popular' ahead of time.

Another way of looking at this is that they're not new mutations that we scramble to develop and test vaccines for, we just roll out the same tried and tested vaccines, but we have to cobble together a different blend some years.

If the above is correct, then I guess the Flu example to answer my question would be: How often is a new variant of Flu (HxNy) discovered that necessitates a new vaccine being developed?


While this is very likely true, this has not been conclusively studied.

Only certain variants have been studied against certain vaccines.


And for every single study of every single variant that has been studied, the vaccine in the study significantly reduces the incidence of severe cases of COVID-19 among the trial group. There is not a single study covering any variant for which this is not the case.

Yes we have obviously not tested every combination of vaccine and SARS-CoV-2 variant. But so far, the evidence that we have supports the working assumption that all vaccines drastically reduce, or in some cases eliminate entirely severe COVID-19 symptoms.


> we have obviously not tested every combination...

I mean, for transparency, we've only tested a very very small subset of the combinations, so it's not very indicative of anything.


Is that true for astra zeneca vs. south african variant?


Yes.


From what I have read, the antibodies are usually the least robust part of the response system.

The real immunity comes from the T cells which will create new antibodies when needed, and may adjust those to variations in the strain.


They are they boots on the ground of the immune system. They just don't stick around more than a few months after infection.


‘Modest evading capabilities’ means there is some protection.

It’s just a glass half full or half empty statement.


It means whatever you read into it, it's not in any way scientific, or even just objectively quantifying an effect.

The current hysteria has really opened my eyes in regards to mass media. We all know mainstream reporting is bad in fields we're experts in, but with the many crazy and often self-contradicting things that are currently reported you don't even have to have any expertise to see the problems in the story.


I agree, unfortunately there have been so many half truths and misleading articles both online and on legacy media that I find myself not knowing what or who to trust anymore.

I have an appointment to get my first jab in 43 hours from now and I am bouncing back and forth between getting it and cancelation.

Five years ago I would not be having these doubts but it seems like everyone has alterior motives.

I wish the social media giants would just stop all the censorship and allow the discussions to take place. I appreciate that they are trying to stop disinformation but I just can't think of one time in the past that the ones stifling free speach have ever been on the right side of history.


If you already have an appointment the only debate should be whether you will need an additional third booster shot in the future if the strain in India breaks out and is different enough.

The key thing you should notice about the COVID vaccine detractors is their inability to distinguish between vaccines and the wildly different technology between the different vaccines, alongside their inability acknowledge the geopolitical hurdles for any of their conspiracies. If a German-company made vaccine is part of an insidious plot, then should you get the Oxford one developed in the UK? If Bill Gates is influencing vaccines in some strange scheme, does the conclusion mean you should trust the Russian Sputnik vaccine more instead due to the geopolitical impossibility of a Bill Gates plot being involved? The absurdity basically cancels itself out, just get the shot you are offered.


So why is there no traditional vaccine? I trust Sinovac. It's inactive virus vaccine, and they ship raw materials[1] to other countries and say "build it yourself" at manufacturers that have no connection to the Chinese government.

Bill Gates on the other hand says these vaccines are too complex and that safety and security issues[2] make it impossible for anyone else to produce these vaccines.

The media keep saying "even mRNA vaccines that are new don't enter the nucleus or alter DNA." Guess which could do that? The viral vector vaccines that have custom DNA run in the nucleus, which then produces the mRNA. This MedCram video[3] explains it better than me. Everything around the messaging for vaccines in mainstream media is so misleading if you look at the science. I don't know how someone couldn't be at least a little suspicious.

I have longcovid btw, I'm not getting the shot. People repeat BS to me like the vaccines will cure longcovid. They offer no proof whatsoever, no plausible method of action, and go off the media narrative how it "could help some people." I'm on longcovid forums, I trust the anecdotal experiences there than anything in the media.

[1] https://en.tempo.co/read/1445856/16-million-sinovac-vaccines... [2] https://www.indiatoday.in/technology/news/story/bill-gates-b... [3] https://www.youtube.com/watch?v=13qT7wLxkvU#t=1m30s


Except that the experience of Chile, and Seychelles in particular is bringing Sinopharm's efficacy into question. I'm very interested in Novavax also but it keeps facing regulatory and production issues.

Both I and my wife had the J&J vaccine a couple months ago. We had a period of about 12, maybe 18 hours of feeling like we had a light case of the flu, and fine since. The J&J and AZ vaccines also use your cells produce spike proteins but do it with a different way (adenovirus vector) than the mRNA vaccines.


I live in Canada so it is age based. I'm guessing it will be either Pfizer or Moderna both of which are mRNA which from my understanding is a form of gene therapy.

My main concern at the moment is: Just as the virus can mutate during it's replicatative phase and produce variants why can't the spiked protien during it's production or the cells producing it mutate also?

If these production cells can mutate or the spiked protiens themselves mutate is it reasonable to assume an autoimmune diseases may result as the cells or protiens accumulate in my organs, limphnodes, fat cells or other areas?

This is an honest concern that I am hoping can be resolved, rather than be dismissed or attacked.


> both of which are mRNA which from my understanding is a form of gene therapy.

That's incorrect, in the sense mRNA does not alter your genetic material.

> why can't the spiked protien during it's production or the cells producing it mutate also?

They could, but they only exist for a short while and don't create new things. When the virus mutates, it can pass the mutation on to the new "child" viruses. Mutations that make things worse (for us) are super rare, so it only matters if there is also some method to preserve the mutation, select the ones useful to the virus, and make more of them. With the vaccine, it only acts for a short time and cannot "spread", so any mutation is immediately lost.

> If these production cells can mutate or the spiked protiens themselves mutate is it reasonable to assume an autoimmune diseases may result as the cells or protiens accumulate in my organs, limphnodes, fat cells or other areas?

Probably not. There is no method for the mutation to become dominant and take over, so you would have a single mutated cell which isnt enough to affect anything. Ignoring that, the vaccine acts for a short time, so stuff wouldn't generally accumulate because of the short time frame where the vaccine is causing spiked proteins to be created. After the vaccine is used up in your body, no more spiked proteins are created.

Note: I am not a doctor, my understanding may be flawed.


The very TLDR response to this is that MRNA is temporary and not self-replicating. Within a few hours of being administered, all the MRNA in the vaccine has been broken down by the body into amino acids. MRNA can't mutate because it doesn't replicate. It just produces proteins.


Slight caveats:

The mRNA in the vaccines have been engineered to resist degradation in the body, and stick around for as much as 2 weeks. Also, they degrade to nucleotides.


Thank You, that is what I needed to hear and it sounds reasonable, what sort of proteins does it produce? Just the spiked ones or longer strands like DNA? Could You also offer up another TL;DR answer as to why the booster seems to present significantly more side effects? Thanks


> Could You also offer up another TL;DR answer as to why the booster seems to present significantly more side effects?

The first one, some of your cells get told by the mRNA/adenovirus vector (depending on if you had Moderna/Pfizer or J&J/Oxford) to make some 'rona spikes. Your immune system amped up a little bit and your cells feel bad for a bit because of having to spew out spike. Your immune system, which is a little amped up, sees all this and starts to formulate things to kill the spikes (antibodies) and starts to send out other immune cells that clamp down on the cells that are making the spikes.

The second shot? Your cells get the call from the mRNA/adenovirus vector and start spewing out spikes. Your immune system recently saw this so it _really_ starts spewing out more antibodies to get rid of the spikes and more of the other cells to get rid of the spike producers. It it is really ready for the fight and wants to make sure you're ready for the fight in the future too.

The negative side effects are your immune system causing parts of your body to do things it doesn't usually do (like raising your body temperature to help kill off cells that are making these "rogue" spikes).


DNA is not a protein, DNA is not a type of protein, DNA is not formed from protein. DNA is not formed using instructions from mRNA, nor is it modified by mRNA. DNA is made up of nucleotides, proteins are made up of amino acids. They are chemically different things.

As every medical expert has been saying for months now, the vaccine doesn't effect your DNA.

The immune response is what causes the side effects, and the immune response is stronger with the second dose (this follows intuitively from immunity being more robust after 2 doses).


FYI DNA, is not a protein.

The mRNA molecules in the vaccine just contain the instructions for the spike protein. https://berthub.eu/articles/posts/reverse-engineering-source... has a good breakdown of what specificly it makes.

To use an analogy to a computer - DNA is like the hard drive (long term storage but slow), RNA is like RAM (short term, degrades easily, but easy to transport and gets info where it needs to go), ribosomes are like the CPU (executes the code in the RNA, outputs a protein). Normally, DNA gets copied into RNA, which instructs the ribosome what protein to make. The vaccine is like inserting a fake message. The ribosomes see RNA and follow the instructions, but the RNA came from the vaccine instead of the cell's DNA. This is one of the reasons why the vaccine is so safe, because RNA just naturally breaks down very quickly in the body.

Booster generally causes more side effects, because the body has seen the spike protein before (from the first vaccine) so it recognizes it faster and mobilizes a more robust response. In a certain sense, its already done a practise run, so the body kicks things into high gear right away.

[IANAD]


This link is indeed a very good explanation of mRNA vaccines, probably the best that I've seen.

After I read it, I noticed that it was the first time anyone had ever tried to explain _exactly_ how these new vaccines worked, like down to the molecular level.

Most explanations I had seen were usually extremely high level (literally just "the RNA gets read by your cells, which then produce the spike protein, then the RNA is destroyed") or used analogies (as you have done here).

I don't consider myself a conspiracy theorist, but I admit I had been harbouring some concerns/fears over these new vaccines. This link is the only thing I have read that actually allayed those fears.

I think there is a lesson here.

I have a feeling that everyone fears stuff they don't understand, at least a little bit.

I know that the high level explanation is technically correct, but here's the problem: Many conspiracy theories are actually _extremely_ detailed. I have personally seen covid conspiracies that appear to be backed up by scientific papers.

This is what the truth is competing against. A basic, high level "ELI5" explanation is never going to convince a conspiracy theorist who is looking at a stack of science papers.

So I think this link is very important, more people need to read and share it.


The side effects you get is your body immune system fighting an intruder. The reason why second shot is typically worse is because your body already produced antibodies so when you get 2nd shot it immediately goes into attack mode.

BTW: different people have different immune systems, and their body reacts differently. I got my first dose in the morning. By afternoon I just felt tired and wanted sleep (I felt like I didn't sleep the previous night). I went to sleep and next day felt normal. For 2nd dose the same thing happened, except I felt like that one extra day. My vaccine was Pfizer.


I had exactly the same reaction to the first dose, except I had muscle pain in the vaccinated arm for 3 days.

Everyone says the second dose is worse although.


The only definite side effect I had was a sore arm after each Moderna dose. I was actually happy that I had at least some side effect after the second dose because until then I wasn't actually sure that I had really been given the shot.

The nurse was a talker, and distracted me from watching what she was doing. I didn't see the shot go in, and I felt absolutely nothing. I only realized it was done when she said I did not bleed at all and didn't need a bandage.

Every other shot I've ever received I felt, but every other one I was also watching when it happened. Now I'm wondering if feeling them was imaginary, something my brain made up because I saw the jab and expected to feel it.


Mine wasn't. I had some very mild soreness at the shot site. I felt well enough to go to the gym 5 hours after my shot.

Not to detract from people who did have side-effects, merely pointing out that it's possible to have none.


There are some pretty significant leaps here, where are these questions coming from? If someone were to say "no, that's not how it works" what would you do? What evidence (and please be specific, none of this "they went to fast" non-answer) would convince you?


Evidence? Specifically? OK I will try.

A list of the variants and their DNA code? Or whatever makes them vary.

A solid explanation of how these variants are more infectious, not just saying that "The numbers show it" but instead what is the real world physical change in the shape or attack vector that makes them more dangerous, or admiting it is unknown but being studied.

True numbers of deaths caused by covid and vaccines, you can't have it both ways and say "They tested positive for the virus and died so it was covid" then at the same time say "yes they got the vaccine but people die all the time, it wasn't nessisarly the vaccine."

A genuine record of which vaccines the well to do have recieved. Eg: Celebrities, Politicians, Billionaires. I suspect there are a lot more Pfizer going in their arms but they are telling the rest of us to take what we can get.

Maybe drop the racist, sexist, political anti white, anti male, anti Trump bullshit for a while in the media, because fighting the pandemic is just so much more critical right now. Instead of being opportunistic assholes and pushing those adgendas while everyone is scared, locked down and having their loved ones die alone?

IDK there is more, like the stuff comming out about Faucci signing off on funding banned research in Wuhan or the 2015 chinese report on weaponizing coronavirii but I think the first couple items on my list would go a long way. And before I catch a bunch more hate Ill leave it there.


For the list of mutations, there is a convenient Wikipedia article [1]. For example, the South Africa variant has mutation E484K which means mutate amino acid 484 from Glutamic Acid to Lysine. It’s just that simple; you could even download a spike protein crystal structure from RCSB and try rolling your own mutations!

Why a mutation improves transmission takes a lot of investigating to understand. I am not sure why you were under the impression that we know the mechanisms. If you type something like “E484K molecular dynamics” you can find a lot of computer simulations trying to investigate the mechanism, this is standard biological research. Of course we E484K you have a mutation from a negative to a positive residue, so that might give you a hint why it’s harder for the antibody to stick.

I can assure you that here in Japan we do not care about Trump. Perhaps we should be more grateful to his good support for the Pfizer vaccine, which is the one we are now deploying at scale (after the government here did their own review of the evidence).

[1] https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2


> why can't the spiked protien during it's production or the cells producing it mutate also?

So now you have a slightly different protein produced by one particular cell for about 20 minutes. Big deal.

The tumor cells in your body right now are already doing a lot worse.



"which from my understanding is a form of gene therapy"

You're the one who is asking SOCIAL MEDIA companies (i.e. Facebook and twitter) to educate you more. "I wish the social media giants would just stop all the censorship and allow the discussions to take place."

Maybe that's the issue all along. Shouldn't have random people and nefarious state actors provide your education, but maybe go out there and read reputable sources, read peer reviewed trial data (The Lancet), read about the success of vaccinations in countries such as Israel.

Not Facebook and Twitter.


Nice try, don't try to argue that silencing information is helping because I should educate myself through approved sources rather than conversations with community. Whats next re education camps? Dont be a bully dude!


Medical experts tend to be more capable of providing correct medical information than "community". Given the misunderstandings you held about incredibly basic properties of mRNA vaccines, you should determine that the people who taught you those misunderstandings aren't good sources of information.


It's not bullying to point out that some information sources are of poorer quality than others, and that social media selects not for information quality, but for flashiness and ability to enrage.


Anyways, just an update to close out this thread. I made the decision to get my first dose of vaccine and today at 2:44PST I joined team Pfizer.

I am still not 100% convinced but a decision needed to be made and based on the information, a large amount recieved here I chose to get the jab.


"Whats next re education camps?"

okay you're just a troll. Got it. Fun...


> acknowledge the geopolitical hurdles

Each of those vaccines come from a UN/WHO member country.

Geo politically power is wielded by globalist financial elites. These elites generally believe the world is overpopulated. Bill himself is well known for his this belief. Bill as an example runs a charitable foundation that only ever seems to make money.

These conspiracies are not constituted of a flat earth and aliens. They are of human hierarchies, corruption, and psychopaths.


Charitable foundations are designed to make money in perpetuity, otherwise their mission is not possible to accomplish. In the US they have to donate 5% of net assets a year and that is practically their only requirement, based on the idea that a diversified portfolio in the broad market increases in value slightly more than 5%. That is not a strong argument to bolster your skepticism.

If your idea is based on the existence of psychopathic financiers controlling organizations that every country on the planet is part of, and every vaccine production as well in those countries which use completely different technology, then you have left no oxygen in your mind for disproving anything. You've now exempted China from any scrutiny, in exchange for psychopathic financiers that would have much difficulty in collaborating with the party and maintaining status with them. You've replaced that with an insidious plot that makes zero sense and at the best requires opportunists to simply seize onto the reality. But that makes zero sense because the mRNA vaccines were sequenced within a week of getting samples in January 2020 because the technology is simply impressive and is the lifetime work of the Hungarian researcher. Ah, so many problems with this idea.


> Each of those vaccines come from a UN/WHO member country.

So you'd be fine with a Taiwanese vaccine then? That's the only country I know of that has significant medical R&D and is one of the few countries not in the UN or WHO.


foh


I have a hard time buying into the over population argument, especially in the west. Most western nations have declining populations and although consumption is much higher there is still such a need for continued population growth in western nations that immigration is used to ensure there are enough younger workers to support the wealthier aging populations.

Now you want to talk conspiracies to conceal or coverup how the virus came to be, I'm all for that but I don't think billionaires want to kill off all their neighbors just so they can have the earth all to themselves. They enjoy the power and control over people and policy too much for that.


>although consumption is much higher there is still such a need for continued population growth in western nations that immigration is used to ensure there are enough younger workers to support the wealthier aging populations

It's because social-security/pension systems are a pyramid schemes that can't sustain themselves without ever growing population. I consider many Western EU countries overpopulated (UK, Italy, etc), Google Maps satellite images also do a pretty good job at portraying at just how overpopulated the earth is. Pop growth every decade is still insane.


>I have an appointment to get my first jab in 43 hours from now and I am bouncing back and forth between getting it and cancelation.

Sorry, what is the downside to getting the vaccine in your mind?


I advocate getting vaccinated (I am myself) but if people don't want to put foreign substances into their bodies, we should respect their choices, especially since the long-term risk profile is unknown (we are pretty sure it's safe, but who can know?)


We can. There have been hundreds of millions of doses administered and we are keeping track of the side effects.


there are some things you can't know without time travel. what happens after having the vaccine for 5 years? 10? The immune system is strange. There are very few mRNA vaccines that have been deployed to date. Can you be sure you aren't, for example, at elevated risk for something like MS? You can't. Again, I say this as someone who made the choice to get the vaccine. The worst thing about conspiracy theories is that some of them are true. If you don't like people being "anti-science", then the one thing you CANNOT do is shove scientifically irresponsible stuff down their throat in the name of expediency.


Cars and certain power plants dump toxic chemicals into the air and occasionally the water supply. Society doesn't give anyone the option to opt out of putting these known toxins in their bodies because we can't. Society either has electricity & cars, thus poisons everyone, or it doesn't. The best we can do is work to mitigate the negative impacts.

We are at the the point where society needs people to receive a vaccine, or it will stop functioning. How much are you willing to personally sacrifice so that someone near you has the option to avoid getting a couple of shots that a billion other people have already received?

Factories can't run at full capacity until people are vaccinated. Our food supplies, specifically meat, are at risk until people are vaccinated. We are going to keep this society of scarcity until ~90% of people are willing to get two shots.


your assumption is that threatening mandatory compliance is better than voluntary compliance. Humans are irrational and sometimes resist doing the right thing when force them to. Surely you have had the experience that being forced to read a book for school has ruined it, or resisted doing something you wanted to do just because your parent made you do it. If instead you work harder to get assent and consent, your vaccination rate might be higher than if you threaten to hammer it in. Especially in a society where voluntary compliance and resistance to authority is in its social DNA, like the united states.


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> But their choices affect me, and, more importantly, those I care about. So no, I don't respect anyone's "choice" to be an unvaccinated asshole, increasing the chance that people I care about will die

I only respect those that choose to be unvaccinated if they:

1. have had adverse effects to a previous vaccination (like the Anthrax garbage they injected into military personnel or have allergies to PEG)

I really thought I had more than one


What about people that personally know those military personnel? By that extension, what about those who know of those military personnel? Can we extend the range of people that are allowed to be skeptical to those that know of the many failed medical experiments done on people?

Are we allowed to be skeptical because pfizer and co are making record breaking profits on an emergency authorized vaccine. That, in the USA, can only be authorized if there are no other approved treatments for covid-19.. meanwhile, the rest of the world is using ivermectin, hcq, etc to successfully treat symptoms? Can we be skeptical of the fact that the pharmaceutical companies clearly have some political influence over the medical field, and have been using that to push this vaccine? Am I allowed to be skeptical of something that is being pushed by companies that have all paid millions in fines over other previous actions? Or am I allowed to have issue with the fact that these same pharmaceutical companies have been caught paying social media influencers to promote the vaccine, while social media companies actively ban people for expressing doubt?

How about expectant mothers and women planning on having kids? There have been reports that menstruation cycles of women and women that have been in close proximity to people recently vaccinated have been adversely affected.


> But their choices affect me

If you and your family get vaccinated, how do their choices affect you?


As far as I know, I haven't had COVID, but other people having it has certainly ruined my year and everyone else's regardless. There's a lot more at stake than just your personal health.


Agreed, but what do you propose? We will never have 100% of people get the vaccine due to either personal choice or medical conditions.


Right now, there is no cost to not being vaccinated, but it does cause damage to society. Its an economic externality. So we should do same thing we do with any other externalities such as pollution: you legislate to bring cost in line with the damage being imposed on others.

I don't think this should mean jail time, but anything from being barred from public spaces like schools or government jobs, to tax penalties, should be on the table in my opinion. I'm all for freedom of choice, but I'm against freeloading. No one should have to take the vaccine if they don't want to, but they shouldn't be able to participate in all the benefits of society while refusing to do their part in keeping that society functional.


>> But their choices affect me

>If you and your family get vaccinated, how do their choices affect you?

I was simply answering this.


Vaccines are not 100% effective, some people cannot take the vaccine (known allergic reactions, immunocompromised, ...) and continued spread of the virus can create new mutations.


It isn't 100%, no. But I am not sure what you are suggesting then.

If you get the vaccine and are still scared and angry at people that may not have received it, there aren't many options for you aside from indefinite total lock-down.


Herd immunity. If enough people get vaccinated R0 gets under 1, and the spread stops by itself also protecting those who cannot get the vaccine or are unlucky that the vaccine does not work for them. They are protected by the herd.


What are your thoughts on abortion


Let's recognize your comment for what it is: unhelpful internet toughguy-ism. You need to regain some perspective. Calling others "treasonous" for this pretty clearly violates HN community guidelines.


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>>>Putting aside the fact that not being vaccinated is a horrible selfish act that hastens the evolution of a more virulent strain and more death.

Rhetoric like that is almost as bad as the conspiracies floating around. Brow beating someone with legitimate concerns is not right.

Im social distancing, wearing a mask doing all the things necessary and successfully I might add to not aquire or transmit the virus. So please dont call me horrible and selfish for contemplating getting an vaccine that has been rushed through trials with no long term data and worse hearing the powers that be, say "It doesnt matter which one you get just get the first one You are offered", how is that a reasonable statement ever?

If You want to know more in depth what my concern is, I wrote it in another comment. Im going to unplug now as my head is spinning and I need to "relax a bit" obviously.

ThankYou everyone for having this frank disussion and not canceling or censoring it(even though it has cost me quite a bit of karma it has given me more perspective and I appreciate that)


> Im social distancing, wearing a mask doing all the things necessary

Those things are emergency measures, that are important, but not anywhere near as effective as vaccines are. They stop things from rapidly spiraling out of control so instead they just slowly spiral. Its a holding action, one with a pretty high cost, not a solution.

> that has been rushed through trials

They've had the same amount of safety testing as other vaccines. With the rollout, they've probably had more real world testing than many vaccines.

> So please dont call me horrible and selfish

You're taking an action that threatens the lives of other people based on fears about personal safety that don't seem based in reality (at least for the pfizer vaccine. If you want to argue that the blood clots for AZ are scary regardless of their rarity, fine by all means).

Most people use the term selfish to describe someone who puts their own well being ahead of the group even when their concerns for personal safety are valid. If their concerns are largely made up, i can't help but think the adjective fits.


Thank you for being better at words than me.


I got the vaccine for solely practical reasons(it's becoming a requirement for international travel). Im not a hero, I didnt do it to save anybody. It has nothing to do with denying science and more to do with the fact that we can look at the same statistic and what you consider an existential threat and what I consider an existential threat are different. I still dont think accusing someone of selfishness is the proper way to go about it.


> what you consider an existential threat and what I consider an existential threat are different

You're argument that not taking the vaccine is not being selfish is that the risk you are taking by forgoing the vaccine is only a threat to other people not a threat to yourself??

> Im not a hero

Obviously not. Nobody here is a hero. We're talking about an injection with extremely low risk of serious side effects, not storming the beaches of Normandy.


They're choosing to become immune naturally instead of pumping an experimental drug into his body.

If they're under 55 and healthy they're actually doing a good thing by letting people who actually need the vaccine get it.

It's arguable that actually getting the vaccine if you're healthy and young is selfish by stopping someone who needs it from getting it.

Think if all the people in India and Brazil had the vaccines the young and healthy are taking in America.


Do you think India has time now for “natural immunity”?


Think if all of the young people in Western countries didn't get vaccinated and we distributed those vaccines to the grandmother's in India who need them.


> legitimate concerns

FWIW, I didn't see any legitimate concerns. I would love to hear a legitimate concern.

All I see is "but I don't know... I'm not sure...". And I just don't get it. facepalm I fully admit this could be due to a lack of imagination on my part. I often suffer from that, especially when it comes to empathy.

> Thank you everyone for having this frank discussion and not canceling or censoring it(even though it has cost me quite a bit of karma it has given me more perspective and I appreciate that)

Bravo, solidly agree. Things will only be broken more when we can't even talk with each other. Glad we can still do that. Whew. And I'll upvote your comments, should you care about the points. :)


You can't really test these things for long term side-effects/damage. Pretty legitimate concern in my book.

Short term side-effects and effectivenes and such are pretty well known by this point


A legitimate concern? Is not knowing or not understanding NOT a legitimate reason for concern? Would blind trust be better? I started my comments on this thread because I found much of the information I have been seeking is a direct result of an almost dogma being thrust upon society on what is OK to say and what is not regarding Vaccines, and when someone does say something wrong they are silenced by bans or deleted/moderated posts.

Cutting out a persons tongue doesn't make them wrong or prove You right, unless the argument is over who has a longer tongue.


> Is not knowing or not understanding NOT a legitimate reason for concern?

No. Because trustworthy information is easy to find and because "I don't understand X" can be used to argue against doing literally everything, including completely ridiculous things like insisting that wifi towers be taken down due to "wifi allergies". Making a decision that harms other people because of your own personal ignorance is not free from criticism.

> and when someone does say something wrong they are silenced by bans or deleted/moderated posts

You've got dozens of posts in this thread that are not deleted and have dozens of people trying to provide you with accurate information to help. There is no conspiracy here. You aren't being silenced.


If variants or strains existed that could avoid the immune system surely it would be evading the immunity of the people in Texas, Florida or the over 50% of other states that have had no Covid restrictions for months... infection rates would be skyrocketing instead of lingering at record lows.

Stop fear mongering.


It is an emergency authorization vaccine. We haven't had the full trials. No one can honestly claim these are safe long term. In fact, they don't. The manufacturers do not assume any liability for you choosing to consume their experimental product.

https://www.cnbc.com/2020/12/16/covid-vaccine-side-effects-c...


If you're in the US, this is one of the dumbest reasons to use against COVID-19 vaccines, since all vaccines have had the same treatment since 1986 via the National Childhood Vaccine Injury Act.


The article I linked discusses the National Vaccine Injury Compensation Program at length. Would you care to discuss the claim in the article that this program has paid very few claims in the decades since it was created? I checked: it is the exact program created by the National Childhood Vaccine Injury Act of 1986. We're talking about the same thing.

tl;dr: the pharma companies don't have to pay you and the government is extremely unlikely to.


That depends a bit on your country.


Assuming you live in the West, we are all taking the same few vaccines. The trials are not complete for any of the big 3. The specifics of the legality vary from country to country. It typically takes nearly a decade to approve a new vaccine.


A major portion of that typical 10 year approval process is running a clinical trial where enough people get sick to have statistically significant results. When the trials for all the EUA vaccines were run last year, COVID was extremely widespread. That dramatically shortened how long trials needed to run to prove effectiveness.


If the trials were comprehensive enough to prove both efficacy and safety, why did they not catch the AZ & JnJ blood clotting issues? One theory is that these problems primarily afflict those under 40 and this population was not adequately represented in the clinical trials.


Blood clots happen at a rate of something like 1 in 100,000 people, the trial had something like 20,000 people getting the vaccine in it. Statistically its not surprising it wasn't caught. That the risk is probably not equally distributed just furthers that.

For the trial to pick up the blood clots, it would probably have to administer the vaccine to at least half a million people if not more (and you would need other people for the placebo arm). If the size of your trial is a significant portion of a medium sized country, you are not really running a trial but just giving out a vaccine.

The trial established it works, and any safety concerns are rare enough that the risk of not just getting covid but getting covid and having severe illness or dying from covid, is higher for most people. There is no 100% garuntees in life, the best we can hope for is showing that the risk is less than the alternative.


Many of us have preexisting immunity. For that population, the marginal benefit of vaccination is zero. People should be informed about the risks.


Not really. If you are talking about pre-existing immunity from prior infection, the benefit may be less, and in fact it is recommended not to vaccinate within 6 months of infection.

If you are talking about innate immunity or cross-immunity from SARS-Cov-1 it's super rare and hasn't been shown to be relevant in most Western countries.

To see the (reduced) benefit even with prior infection just look at the numerous reports of re-infection, be it with a mutated version or otherwise, as well as the numerous reports of prior infected subjects with no or very little antibodies after a couple of months (not the full picture but still).

> People should be informed about the risks.

Show me one vaccine/medication where people were more informed than about the current Covid vaccines. We are at the point that for most folks it's riskier to drive to the vaccination appointment by car then the actual vaccination.


> it is recommended not to vaccinate within 6 months of infection.

24/7 ads and encouragement for people to get the vaccine, almost to the point that it's a moral virtue means that tons of people are getting the vaccine, even having recently caught covid-19.


You can't get the vaccine without anamnesis/checking your medical history, and one item is prior infection.


Not in the US. I got my first vaccine shot, Moderna, with no medical consultation at all. Nobody asked me if I'd gotten Covid already.

And I had never heard about this six month interval until this moment.


Interesting, could you elaborate more?

The six month interval is not a universal truth but the recommendation by the German regulator [1].

[1] https://skeptics.stackexchange.com/questions/50476/do-the-co...


What would you like me to elaborate exactly?


Just interested how the vaccinations were done where you got it, small/big city, who administered it etc...


In New York City, at a large pharmacy chain, administered by a pharmacist. They're done like this, or at government run centers. The cost is handled by the government.


It's also riskier for most folks to drive a car than to catch Covid. I agree that people should look at their specific case and do honest risk/benefit analysis.

Most of what I've seen, however, feels more like herd mentality behavior based on one's political leanings. Or people feeling they genuinely don't have a choice, given impending requirements and restrictions from their local governments and employers.

Edit: not sure why I'm being downvoted. It should be common knowledge at this point that people in their 20's, 30's, and 40's have a higher risk of automobile accident, suicide, drug overdose, etc, than of covid death.


As a European I do not understand what vaccination has to do with political leaning. It's even stranger that in the US pro-life (abortion) seems to correlate with pro-choice (vaccines)?

I do understand however that society as a whole says "if you are not willing to take a negligible risk for us, we are not taking risks for you".


We are in an unfortunate state of hyper-polarization where, if one side advocates something, the other side feels compelled to reject it. Unfortunately, this has even extended into medicine. Many such cases! Sad!


I estimated that my risk from getting infected was similar to the lifetime risk of driving.

If I could get a shot that protected me from car accidents, I'd do that too.


The shot doesn't last a lifetime. You'll need two shots a year, at minimum. Third and fourth booster shots needed in the fall are already being discussed.


People are informed about the risks.


You can't know what kind of pre-existing immunity, if any, you have against covid.


Including after vaccination? If no, why is that different than infection?


No, not including after vaccination. When people speak about pre-existing immunity, it's most of the time covid deniers saying there "natural" immunity and vaccines are useless or harmful.

(Of course there is also valid discussion of pre-existing immunity, but the more nuanced messages are not as common.)


Vaccine advocates like yourself can never explain why infection doesn't imply immunity while vaccines do.

Sinovac, the Chinese vaccine, is only 50% effective. Pfizer and Moderna are much more effective. J&J is somewhere in between. This is widely accepted but no one seems to ever ask: if I was sick a month ago, where does it fall in that scale?

The point of vaccines is to give your immune system a good enough idea of the pathogen, so that your body produces antibodies. Actually contracting the disease does the same thing, unsurprisingly.

So the question is how effective is natural infection of COVID-19 at preventing future infection? Surely it's better than Sinovac, a coin flip. No? Do you have any scholarship about this I can look at?


What? Of course infection induces immunity in case of covid, about on par with mRNA vaccines like Pfizer and Moderna.

https://www.nih.gov/news-events/nih-research-matters/lasting...

You don't have similar immunity efficacy studies for actual covid as hou have for vaccines, because infecting people on purpose would be unethical.

Note that your wording "coin flip" isn't right for Sinovac, either. 50 % efficacy is not huge but it is still beneficial on population level.


> WTF? Why? You have a free, safe, live-saving vaccine being offered to you! Why would you not take it??

People have real distrust of the system that produced the vaccine and even distrust of the media that purports this disease is so deadly.

I know from your perspective scepticism is hard to understand, but it's not that God tells me science is fake or anything so outlandish. I genuinely don't trust the corporations and government selling me the story of the disease and now the vaccine, and it should be allowed that people question these institutions.


> People have real distrust of the system that produced the vaccine and even distrust of the media that purports this disease is so deadly.

WHY??? Why do they distrust the vaccine?? Anything? Any possible reason? It's probably the safest vaccine ever made. I. DON'T. GET. IT.

Do others not hear the ambulances? Do they not see the overflow from the hospitals? Are the dead bodies some sort of elaborate deep fake?? Has the whole world gone mad???

Brother, I love skepticism. It's healthy. It's *good*. I don't blindly trust corporations or the government, as far as I'm concerned the former only wants profit and the latter only wants power.

But that's got nothing to do with it, from my perspective.

When your house is on fire you don't debate the motivations of the fire department. You put out the fire first, and THEN have time for dithering and analysis.


> WHY??? Why do they distrust the vaccine?? Anything? Any possible reason? It's probably the safest vaccine ever made. I. DON'T. GET. IT.

I'm getting my 2nd shot this week, but both mRNA and modified adenovirus vaccines have never been used for mass vaccinations before. The history of medicine is litered with interventions that were seen as totally safe and wonderful and lead to terrible consequences after some time. Push towards massive adoption of an intervention sets off my alarm bells.

All that said, personally, it seems the unknown long term risks of vaccination outweigh the more or less known risks of covid both on an individual level (I don't want to get it) and a community level (I'd rather like community spread to stop, so I can go back to being a hermit by choice); but if community spread wasn't happening near me, I would be happier not trying new medicine within a year of development.


> I'm getting my 2nd shot this week, but both mRNA and modified adenovirus vaccines have never been used for mass vaccinations before. The history of medicine is litered with interventions that were seen as totally safe and wonderful and lead to terrible consequences after some time. Push towards massive adoption of an intervention sets off my alarm bells.

These events sadly happen and there will always be unknown unknowns, not only, but also because of human hubris. However, it seems you are overestimating the prevalence of such events and extrapolating that to the current situation. If you take a birds-eye view on medical progress over the last 50-100 years says, it's just incredible.

> All that said, personally, it seems the unknown long term risks of vaccination outweigh the more or less known risks of covid both on an individual level (I don't want to get it) and a community level (I'd rather like community spread to stop, so I can go back to being a hermit by choice); but if community spread wasn't happening near me, I would be happier not trying new medicine within a year of development.

Agree with you. From what we know today it seems that the unknown long term risks of the vaccines are a subset of the unknown long term risks of Covid.


I know this is an inflammatory topic that evokes visceral feelings but.. you should be aware that when you are trying to change someone's mind, aggressive arguing like this is much more likely to make the other person believe what they already believe more strongly (i.e. the opposite of what you want).


Go to your local hospital and see for yourself how deadly the disease is.


I can't just walk in.

That said I know several people that have had it. Some elderly with existing conditions. Worst case was my aunt who got pneumonia from it. She's in her mid sixties and diabetic. She was in the hospital for a week.

Was in the emergency room with my son a few months back, not overflowing or anything, but I wasn't there to track Covid cases.


In Germany they showed the whole shift of an covid nurse on tv. They really should show something similar in every country. Gives you a lot of perspective.


Do you know what the name of this program is? I'd be interested to see if I could find it online somewhere.


Pflege ist #NichtSelbstverständlich | Joko und Klaas

Edit: It's available on a german video on demand service maybe a vpn will work for you https://www.prosieben.de/tv/joko-klaas-gegen-prosieben/video...


my coworker's parents caught it. they were in their 50s. the mom became severely ill and was hospitalized for weeks. the dad died. my coworker himself got it and was mostly fine.

it's really hard to intuit how wildly variable this disease is when you only have a couple personal data points and distrust/feel detached from the statistics being reported, but it's real.


Going only off personal experience can really skew your perceptions. If I'd've been living away from home at the time, and thus avoided catching it, it would've completely changed the colour of our experiences:

* Mother, 50s - metallic taste for two weeks, loss of appetite, some fatigue * Father, 50s - sore throat for a week * Sister, ~20 / Grandmother, ~80 - both had similar symptoms of fatigue, body aches, sore throat, feeling hot/cold, some change to taste * Grandfather, ~85, multiple pre-existing conditions (COPD, heart failure, prediabetes, history of TIAs) - only reason we knew he had it was due to a positive test

Going off those alone, it seems unpleasant but not too dire. Then you add me in:

* Me, 30 - same symptoms as sister/grandmother for about a week, then ten days in the ICU after my O2 sats dropped to 78 overnight (and remained in the 80s on oxygen). Narrowly avoided ventilation as I responded to CPAP.

Suddenly it seems a lot more serious.


> Was in the emergency room with my son a few months back, not overflowing or anything, but I wasn't there to track Covid cases.

In most (all?) hospitals, Covid cases are separated from general emergency because you don't want your emergency room transformed in a constant cluster.


I think parent's advice is solid. Covid sits at this sweet spot where it's not that bad for young folks, but it's easily transmissible and mortality increases exponentially with age. Which means certain demographics will be hit disproportionally hard.

At the same time only a small fraction, say 10-20%, of the population has had a Covid infection. So while some are hit hard, at the same time it might not affect you and the people around you too much.

Maybe ask your family doctor/general practitioner, or you have a nurse in your network or wider family, or somebody working in a hospital or care home? Also speaking to older folks like parents or grand-parents can be helpful to get another perspective.


Well I've had two family members die from it and another on death's door in the hospital and now is losing her hair months after recovery, so anecdotes can go both ways.


I'm also not claiming anecdotes are what are making up my mind. I was simply responding to the suggestion that I walk into a hospital.

I too believe that anecdotes are poor evidence at best, and I completely believe others have had 180* experiences from myself.


If you're under 55 and are healthy your chances of dying from this virus are basically non-existent.

You'll get a sniffle/fever for a few days and then be immune.

Don't put an experimental drug into your body for no reason.

Anyone who says variant or strains are a problem has merely to look at over 50% of the United States with no covid restrictions for months who are at record lows of infections and with minimal vaccines.

The variant or strain problem is a nothing burger.


Tell that to my 30-year-old sister - who still has migraines and extreme fatigue a year after catching covid, who was healthy, an avid runner, and had no preexisting conditions before.


The article that I saw today was contradicting itself. In one place it said that there are 3 mutations and that vaccine might not work on it, and in another place that it should.

My understanding is that at this point we don't know yet. The actual testing would probably require a vaccinated person to be exposed to that strain.

Chances are that vaccine is probably still fine.


yes, as with all the other variants they should just say "we don't know yet, let's find out", but instead they defer to some scientific language of "no evidence that it protects" that the general population cannot relate to


Can you actually link to a source?


There was a WHO press-conference about a preprint, and more information is coming this week.

That is the totality of information.

https://www.washingtonpost.com/nation/2021/05/10/coronavirus...

https://www.biorxiv.org/content/10.1101/2021.05.04.442663v1

I don't have access to the FT article as it is paywalled, but some less meaningful sources have summarized it and use the "modest evading" phrase.

As I don't care for the conversation as I lost all energy going over this stuff last year when the same thing happened, a preprint is not peer reviewed and is necessary to become peer reviewed. Hundreds of thousands of people will die before that happens. Make your own decisions.


well ... there isn't the internet. this news is from Nature - very reputable. what is your other source? the daily mail?


Both sides are represented, that’s a good thing. The thing I hate is that the side people tend to agree with will be automatically assumed right and the side they don’t will be fake news.


So, then I would assume this means people with antibodies from the initial wave of infections are also protected


Not necessarily [1]. COVID vaccines particularly give you far higher neutralization titers than a prior infection.

[1] A glaring counterexample to your hypothesis is Brazil (Manuas) where prior infections (as high as 60%) didn't stop the P1 variant from ripping through.


> [1] A glaring counterexample to your hypothesis is Brazil (Manuas) where prior infections (as high as 60%) didn't stop the P1 variant from ripping through.

The prior infection estimates for Manaus were simply wrong. They were based on a paper that "adjusted" the observed seroprevalence rates upward by a factor of ~3x. The parsimonious conclusion is that these corrections were too aggressive and ended up over-estimating infections. See Figure 2a in the paper, here:

https://pubmed.ncbi.nlm.nih.gov/33293339/#&gid=article-figur...

It is a "glaring" example only of how the low editorial standards of major journals during this pandemic has led to a wave of confusion amongst the public.


Conversely, we can make the same argument in the opposite direction with the example of Seychelles, which in spite of the highest vaccination level in the world, is still seeing significant growth in cases: https://www.bbc.com/news/world-africa-56992121

Apparently they're using 40% Astra Zeneca, 60% Sinopharm; hopefully the issue is simply the latter being ineffective. But as all the success stories with vaccination have also had very significant numbers of deaths with covid, we may need significant levels of natural immunity in conjunction with vaccine immunity to actually get cases to decline.


I don't see how anywhere could get to count as a "success story with vaccination" under your criteria while also not having "significant numbers of deaths with covid" and so I don't think you end up with a meaningful observation.

New Zealand had zero community cases without vaccination, during 2021 its vaccination programme has only covered some front line workers and very high risk people, and it still has zero community cases. Is that "success"? Is it "not success" ? How would you tell?

Whereas in my own country about two thirds of adults have had at least one jab, but still people are dying every single day from COVID-19, just much fewer than an the height of the pandemic here. Is that a success? Not a success?

One of the reasons New Zealand was so slow? With zero cases they had no reason to do Emergency Authorization. So they didn't. The Pfizer vaccine they picked got the full (albeit accelerated) approval process that any other medicine would get. This behaviour would be crazy in a country like the US with thousands dying, but it made sense in a country where most citizens have negligible risk day-to-day.


> I don't see how anywhere could get to count as a "success story with vaccination" under your criteria

I think you're reading my comment incorrectly. I'm not promoting a criteria. I'm just stating the facts: we may find out that vaccines alone simply can't stop covid from infecting - and maybe even killing - large numbers of people.

Obviously, if that is true to a sufficient degree, lockdown may prove to have been pointless.

> How would you tell?

New Zealand will most likely find out how successful their vaccination program was when they open their borders to the rest of the world.


The AstraZeneca and Sinopharm vaccines have similar efficacy: they're about 80% effective at preventing symptoms. They're even more effective at preventing serious illness and death.

The Seychelles is still 40% unvaccinated. Even people who are vaccinated have some chance of getting infected, though if they get infected, their chance of showing symptoms is lower, and their chance of ending up in the hospital is much lower. It looks like the people testing positive in the Seychelles are mostly unvaccinated, and that the people ending up in the hospital are even more likely to be unvaccinated. But there's not enough information in the BBC article to judge just how effective the vaccines have been in the Seychelles.

The BBC article does contain one falsehood:

> In April, China's top disease control official said the efficacy of the country's Covid vaccines was low, although he later insisted his comments had been misinterpreted.

George Gao did not say this. He gave a talk at a conference on vaccines which was blatantly misconstrued by a "researcher" at an American think tank, the Council on Foreign Relations. That misrepresentation then got spread by the media. All George Gao actually said was that researchers should consider ways of increasing the efficacy of vaccines that have lower efficacy. He didn't name any specific vaccine or any specific country. He proposed the same sorts of measures that are being considered for other vaccines, such as the AstraZeneca shot: delaying the second dose, mixing vaccine doses, etc. This got twisted into an "admission" that Chinese vaccines have low efficacy. It's too bad to see that the BBC is still repeating this false claim, weeks later.


Seychelles has vaccinated 68.5k of its 98.5k population. [Around 25% of its total population](https://en.wikipedia.org/wiki/Demographics_of_Seychelles) are 0-17, so maybe 75k max 18+. Over 90% of adults are vaccinated and less than 7k remain unvaccinated.

Seychelles just reported 1800 cases for the last week or 1.8% of its total population. This equates to 6 million cases in the US or more than 800k per day, a number never approached.

> It looks like the people testing positive in the Seychelles are mostly unvaccinated

It stated that 1/3 were in fully vaccinated and the rest were in partially vaccinated or unvaccinated. There are now 60k that are fully vaccinated, leaving just 8.5k first-dose only. The article was written before the 1800 cases dropped a couple days ago.

More data is needed for hospitalizations and deaths, but as it stands now, it does not look convincing for the vaccine. It's likely more cases will continue to come over the next few weeks, even more than the record breaking prior week.

Seychelles and other island nations that had no major covid outbreaks before vaccine launch (only 500 cases prior and 7.5k since) are the best real life settings we have for vaccine efficacy. For much of the rest of the world, a huge number of people were already infected before vaccine launch, making it difficult to separate out the effectiveness of the vaccine.


Unless you calculate an actual efficacy, the above numbers are not very informative. What efficacy is implied by the numbers?


It would be easier believing you if you didn't spend all your time on this site defending China...


Just have a look at the (non China) data from a real world Sinovac vaccination campaign yourself: https://www.minsal.cl/wp-content/uploads/2021/04/Effectivene...

I see 67% effectiveness of preventing symptomatic cases for Sinovac. I'm not sure where the 80% comes from, they could be talking about AstraZeneca.


The Seychelles has been using a Sinopharm vaccine, not the Sinovac one. They're similar vaccines, but there could be slight differences. The WHO just approved a Sinopharm vaccine (called "BIBP"), and has stated,[1]

> A large multi-country Phase 3 trial has shown that 2 doses, administered at an interval of 21 days, have an efficacy of 79% against symptomatic SARS-CoV-2 infection 14 or more days after the second dose.

There are two different Sinopharm vaccines, but I think that BIBP is the one being used in the Seychelles. And yes, as you note, the Phase III studies were conducted outside of China. In order to conduct a Phase III study, there has to be community transmission of the virus, meaning that Phase III trials are impossible in China right now. You would get the same result for the vaccine and placebo arms of the trial: no infections.

1. https://www.who.int/news-room/feature-stories/detail/the-sin...


> A third of the active cases involved people who had had two vaccine doses, the country's news agency said.

> The rest had either had a single dose or were unvaccinated.

So ~66% of the cases were from partially or unvaccinated people.


> COVID vaccines particularly give you far higher neutralization titers than a prior infection.

Do you have a source for that?



The study itself says that the immune response to the vaccine is not as diverse as a natural infection. That's how the study tried to figure out who had been infected:

"Natural exposure induces a dominant Ab response against the nucleocapsid protein (NP), but since NP is not in the vaccine, there is no vaccine induced response against it. In this way vaccinated people who had a prior natural exposure can be classified because they have Abs to NP."

Simply looking at one aspect of immunity - detectable antibodies in the blood - is a very incomplete way of looking at the overall level of protection. For example, it's well known that mucosal immunity is important, and injected vaccines have a hard time inducing that kind of immunity: https://theprint.in/opinion/why-a-mucosal-covid-vaccine-has-...

It's also concerning that there is evidence that while people who have been vaccinated are much less likely to be infected. If they do get infected, they are more likely to be infected with one of the variants than unvaccinated: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA728463

The immune response developed to our vaccines is quite specific - they only generate the spike protein - which leads to a much less diverse response than a natural infection.

Finally, the study you quoted can't really compare apples to apples anyway, as it's defining prior infection as simply having some level of antibody response, without considering how mild or severe those infections actually were.


High NAbs titers in the blood against spike will almost certainly be protective and even in the absence of sterilizing mucosal immunity will confine any infection to the upper respiratory tract.

I'm nowhere near as concerned about a variant infecting my upper respiratory tract as I am with being unvaccinated and having any of the variants attack my heart, kidneys, lungs and blood.

The use of spike was also not a mistake. Attempts to produce vaccines against NP for SARS-CoV-1 produced signs of ADE, so that is why everyone is using spike-only (other than the few inactivated virus vaccines).


> Simply looking at one aspect of immunity - detectable antibodies in the blood - is a very incomplete way of looking at the overall level of protection. For example, it's well known that mucosal immunity is important, and injected vaccines have a hard time inducing that kind of immunity: https://theprint.in/opinion/why-a-mucosal-covid-vaccine-has-...

I have not seen an actual credible claim that injectable vaccines can’t produce mucosal immunity. IIRC the HPV vaccines seem to generate strongly protective mucosal immunity. The opinion piece you linked seems off, too: the mRNA vaccines and (possibly to a lesser extent) the viral vector vaccines do seem to prevent most infections.

But it’s definitely true that antibodies in the blood are an incomplete picture. There are also memory B cell and all kinds of T cells.


> It's also concerning that there is evidence that while people who have been vaccinated are much less likely to be infected. If they do get infected, they are more likely to be infected with one of the variants than unvaccinated

That's not "concerning"...it's a truism. You've made those people immune to the wild-type strain. If they're going to get infected, it's going to be to a variant. You're still missing the denominator (i.e. how often does it happen?) and the most important question: how serious is it when they do get infected?

So far, the answers are "not often", and "not serious", respectively.


The spike protein is what is in common between all the variants. Getting a more diverse response doesn’t mean better protection.


>Natural exposure induces a dominant Ab response against the nucleocapsid protein (NP), but since NP is not in the vaccine, there is no vaccine induced response against it. In this way vaccinated people who had a prior natural exposure can be classified because they have Abs to NP."

>Simply looking at one aspect of immunity - detectable antibodies in the blood - is a very incomplete way of looking at the overall level of protection

You seem to have no idea what you are reading. Of course vaccines aren't going to have antibodies against the nucleocapsid -- they only generate antibodies against the spike! The vaccines only ask the human body to develop immunity to the spike!

And you know what actually neutralizes the virus? Mostly antibodies against the spike because that is where all the important parts of infecting a cell originate from.

>For example, it's well known that mucosal immunity is important

You are right about mucosal antibodies -- but your statement is also proving to be false as more research comes out. The latest research shows IgG antibodies from vaccination in the mucosal regions too. Apparently our nose is not just waiting for IgA from a natural infection (https://www.medrxiv.org/content/10.1101/2021.05.06.21256403v...)

>It's also concerning that there is evidence that while people who have been vaccinated are much less likely to be infected. If they do get infected, they are more likely to be infected with one of the variants than unvaccinated

You also completely misrepresented this (and frankly, it's disappointing you couldn't even link to the actual publication -- it's https://www.medrxiv.org/content/10.1101/2021.04.06.21254882v...). The framing of this is disingenuous. Vaccines provide nearly complete protection against the non-variant form of COVID-19. They provide a little less protection against variant COVID-19s. Your non-protected human body is the same way -- it's more likely to get a variant too. It isn't that if you get infected after vaccination, it's because you were more susceptible to variants, it's that everyone is more likely to get one of the variants. Your risk is still minimized way more than than if you weren't vaccinated!


They wrote:

> The immune response developed to our vaccines is quite specific - they only generate the spike protein - which leads to a much less diverse response than a natural infection.

Which tells me that your response of:

> You seem to have no idea what you are reading. Of course vaccines aren't going to have antibodies against the nucleocapsid -- they only generate antibodies against the spike!

is wholly inappropriate as they clearly know what you are using as a rebuttal and makes me wonder if you are the one with no idea of what you are reading!

Perhaps take a second to read the person's comment more thoroughly before being rude, which I see you've continued with in the rest of your comment. It's a discussion, not a fight, try to add your thoughts in a better way, please.


The N protein is evasive, I do not believe your body can mount an effective (neutralizing antibodies) defense. But I guess you are right, your body can still fight it which is overall better than just fighting off the virus with vaccine protection


I wasn't making any statement about natural immunity versus vaccine provoked immunity, but the attitude and sloppiness of the commenter and comment I replied to. I have no idea if one is "better" than the other.


> glaring counterexample to your hypothesis is Brazil (Manuas) where prior infections (as high as 60%) didn't stop the P1 variant from ripping through

This says nothing about the strength of a previous infection. It very plausibly just says that R > 1.7, ie it is infecting the remaining 40%.


are you sure about the infecting the remaining 40%. In every article I read, they specifically mention re-infections in many cases.


mRNA vaccines produce antibodies targeting just the spike protein( S protein). There are other proteins on the virus like the M protein. Antibodies produced during an infection may target other parts of the virus so you can’t compare the two.


Isn't it the spike protein that is usually different between these variants? In that case antibodies that target a different part should even be more effective.


The vaccines target specific (and multiple) regions of the spike protein, so a given mutation of the protein is not likely to make a vaccine null and void (hence the current success of the vaccines against variants). A "natural" COVID infection could lead to similar protection, or less; but it's not likely that a natural infection gives you some kind of AAA protection. Being infected can also hurt you, after all. There is literally no downside to receiving the vaccine if you've already had COVID, so I would encourage everyone to get vaccinated regardless :)


It's not quite no downside. It may be inconvenient (especially if you live in a country where you can't necessarily get time off work to seek medical treatment) and you're quite likely to have a sore arm. Some people experience fever, headaches, or other annoying symptoms for a day or even longer. I had a powerful craving for a kebab, at like 0400 when all the kebab shops are closed, maybe a coincidence, but maybe not. If you told me I can get a free Coke, but I have to take an hour off work and then my arm will be sore for two days, I think I'll pass on your "free" Coke.

Now, of course the excellent chance of becoming immune to a respiratory infection that's killing loads of people is a much better offer than a Coke. So I agree people should take up this offer, get yourself vaccinated - but we shouldn't claim "literally no downside".


>I had a powerful craving for a kebab, at like 0400 when all the kebab shops are closed, maybe a coincidence, but maybe not

to be fair, you could have scheduled your shot at a different time so the kebab shops would have been open amirite


I totally take your point, but frankly, I’m not interested in convincing someone who would avoid the vax because of the (minor, very manageable) side effects. I’ll let the public health folks tackle that one ;)

I honestly hoped I had more side effects! You know you’re not getting sick, so a mild fever? Kind of a perverse pleasure.


With the AstraZeneca vaccine (and presumably J&J would be similar) a consideration is that the side effects you see might actually have to do with the platform itself.

Unlike the mRNA platforms, these vaccines use an existing virus to make the spike proteins. Specifically, an Adenovirus (so the sort of thing that might be implicated in some colds) but which ordinarily thrives in Chimpanzees instead of Humans, so they can have confidence you aren't immune to it already. The virus is altered to tell human cells to make the protein chosen by the engineers (for COVID-19 this was the spike protein from the SARS-CoV-2 virus); and not more copies of itself, once the copies in the vaccine injection are cleaned up (typically a few hours to a few days) the virus is gone, so you can't "catch" the virus.

But of course your immune system has no particular reason not to destroy this (harmless) Chimp virus meanwhile, it shouldn't be in your body, so it's every bit as much a target as the spike proteins we want immunity against.

Thus, it's certainly possible any fever one particular patient suffers is a side effect from their immune defence against this poor harmless chimp adenovirus, and nothing to do with SARS-nCOV-2 or its spike protein. No way to tell for sure I believe.


Not the OP, but to be fair the exact quote was:

> no downside to receiving the vaccine if you've already had COVID

So I assume that this means that there is no difference in potential unwanted effects between persons who have already had COVID and who have not.


Fair


20 million people tested positive before vaccines became abundant. Let’s stay on the topic of those people protection levels :)


So are mRNA vaccines are more effective than conventional (i.e. dead virus) vaccines and natural immunity because they target a smaller set of proteins, effectively telling the immune system exactly which protein to produce antibodies for?


Yes, but it also is the part that the virus uses to bind to and enter a cell. It can mutate to a certain extent, but there are limitations to how much can change about it without destroying its ability to actually infect individuals.

On the other hand, there is some concern around the phenomenon known as "original antigenic sin". Its unknown if it is or will ever be an issue with Covid, but it essentially means that for some viruses (such as the flu), your immune system imprints on a virus the first time it encounters it, and more heavily relies on immunity for that particular virus than new antibodies for variants of that virus later on. This leads to the body mounting a sub-optimal defence against new strains of the virus (which is in part why we have yearly flu vaccines that don't offer amazing protection). There is some concern that there is a possibility that over time covid will continue to mutate and those whose initial infection was natural won't have as protective immunity as those who were vaccinated first, precisely because the vaccine only targets the spike protein and not the entire virus:

"Still, Hensley isn’t worried about imprinting — or at least not among people who have been vaccinated with mRNA vaccines. The very strong immune response generated by the Moderna and the Pfizer-BioNTech vaccines should override any imprinting impacts as SARS-2 mutates, he said. Hensley worries, though, that people whose immunity to the virus comes from infection, not vaccination, might have more difficulty handling variant viruses because of imprinting effects.

David Topham, an immunologist at the University of Rochester Medical Center and director of the New York Influenza Center of Excellence, also envisages that possibility.

He noted that, in the earliest stages of SARS-2 infection, the immune system mounts a response to a portion of the spike protein called S2. Later, the immune system focuses its attention on other parts of the spike, notably the part of the protein that attaches the virus to cells it invades, known as the receptor binding domain.

It’s not yet known if the early focus on S2 — which doesn’t change much from virus to virus — will blind the immune system to the changes elsewhere in the spike protein, the changes updated vaccines would be trying to teach the immune system to respond to, Topham said.

Topham doesn’t think this will be a problem in vaccinated people, because of the way the vaccines in use have been designed. The spike proteins they trigger production of appear to hide the S2 region, he said. The immune system can’t fixate on something it doesn’t see.

For people whose immunity comes from infection, Topham sees three possible scenarios. “It can be a problem, because the immune cells specific for S2 outcompete immune cells against other components of the spike protein that you really need in order to get protection. It can be inconsequential in that eventually the responses to the other parts of the protein catch up and it doesn’t matter. Or it could actually be a benefit because it gets the immune system revved up more quickly.”[0]

[0] https://www.statnews.com/2021/04/16/next-generation-covid-19...


No. Antibodies to an infection can be a variety that target different parts of the virus.

The vaccine produces antibodies to a specific stretch of the spike protein. So everyone who has the Pfizer vaccine has a similar (but not identical) group of antibodies.

Those infected with Covid-19 have a more diverse set of antibodies that may or may not protect as well against varients.


Interestingly, the mRNA vaccines produce superior immunity compared to getting infected, due mainly to the two dose regimen. For similarly long-lasting natural immunity you'd probably need to get infected with covid twice.


There's also the benefit that with the mRNA vaccines (and the adenovirus vaccines as well), your body is developing antibodies specifically for the spike protein, which is highly conserved. Your body's immune response to actual covid may, just by chance, focus on a less strongly conserved target.


I was under the impression that it's the other way around; spike protein is not conserved between variants [1]:

https://theconversation.com/new-coronavirus-variant-what-is-...


That article is explaining that it's particularly worrying that some variants do have changes to the spike protein, not that this is common (it isn't).

Mutation causes random changes, the selection process eliminates those that render the mutated version less fit. The focus on the spike is because most random changes to the spike also make it useless, the virus becomes impotent. Such mutations won't thrive of course, and so we hardly see them at all, but they are happening.

In contrast, many random changes elsewhere might not prevent the virus from working. They might say, make it less able to survive outside a body, which would give it a disadvantage against variants that don't have that change, but if they also mean the immune system of a previous host doesn't recognise them, that's a big advantage to counteract that. We see lots of these variants because they "work", but since the spike is the same existing vaccines ought to be effective.

So this is why it made sense to focus on the spike, even though as this article shows it isn't a magical panacea.


If you track each and every mutation as a variant, then here are thousands of them. Changes in the spike protein have the largest effect though, so we track those specifically, and clusters of changes to the spike protein are what get official designation as variants. Because that’s what we care about.


Do you have a source for that?


My wife is an immunologist who works on this at BioNTech. She explained it to me that this is expected and the data matches it. She explained why as well but there's a big gap in my undergrad-level understanding of bio and her phd + years of experience in the field, so it went way over my head I'm afraid.


What about the probability from having had a very bad infection?


the big diff between a vaccine and a previous infection is that the vaccine doesn't damage your body in the process of training your body to attack it.

Covid can wreck havoc on your body and leave it in a weaker state.


20 million people already had the virus. I’m one of them. Are we the red headed step child that we have forgotten about?

Let me change the perspective: when I get the flu because I stupidly did not get the flu shot that year, I don’t rush out and get the flu shot after the fact. I’m wondering why I would do the same with this vaccine when there are lots of evidence that first rounders are not likely to be infected even by variants (assuming low viral load)


I've been asking this same question and have yet to hear a very convincing answer.

The best answer I've heard is: it will give you "extra immunity".

Which begs the follow on question, if we're so concerned about topping off our immunity, why shouldn't people get vaccinated and revaccinated every month or two?


> BioNTech CEO Ugur Sahin told CNBC last month he is “confident” the company’s vaccine, which was developed together with U.S. drugmaker Pfizer, is effective against the variant from India.

https://www.cnbc.com/2021/05/11/india-covid-explainer-what-w...


"effective" like "protects" are nebulous terms.

The reality is that vaccines target multiple proteins and one protein mutation usually does not even evade that specific protein from matching (much).

It's a sliding bumpy scale with each mutation reducing the effectiveness of the vaccine some small random amount.

It's very likely that all the current vaccines confer sufficient immunity to all current variants to a degree that will prevent serious Illness and likely even transmissibility.

But the real takeaway here is that, like flu, we are looking at yearly covid boosters for everyone for years to come.


I hate headlines that try to tell me how I should feel about something. It seems like it would be equally informative without the “worrying”.


"worrying" is an identifiern of the variants.

If it protects against the 2 least significant variants, that's less interesting of an article.

Unless it protects against all variants the headline would likely be inaccurate without the "worrying" qualifier.

I could agree with a criticism that "worrying" should be replaced with a better identifier of the specific variants being discussed, but I don't have a replacement proposal. And dropping the word "worrying" seems like it might be factually wrong (it also might not be, I don't know)


Epidemiologists use the term "variants of concern", so maybe "concerning" would have been a better word. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/vari...


There are hundreds if not thousands of variants by now. The ones that matter are the ones that spread more easily and/or make people sicker, aka the "worrying" ones.


It's not telling you to whom it is worrying. You made the mistake of assuming the headline meant "to you" but it is not stated. It is certainly worrying to someone.


They probably should have said "variants of concern".


Great news. Wish we could see the impacts of pfizer in the indian population against some of the other variants coming out there (and helping them out as well).


How does the Moderna vaccine compare?


Since it’s based basically on the same mRNA technology (and has the same reported efficacy) I would assume it works as well as the Pfizer one. No hard data to back this up, though.


This is a false assumption as they have different mRNA instructions. As you point out, wait until there is data and treat the vaccines independently.


> This is a false assumption as they have different mRNA instructions

Depending on what you mean by “mRNA instructions” that might not be the case. Both vaccine mRNAs encode exactly the same variant of the spike protein.


yes, but no. while it’s technically the same protein, the way it was optimized differs (not by much but it’s different). the vaccine itself has the instructions to produce something that resembles the spike protein (to which your immune system goes in overdrive and generates antibodies)


> while it’s technically the same protein

Not technically, it’s actually the same protein/polypeptide sequence in both cases, 100% identical, including the proline mutations that stabilize the prefusion conformation. You can check that easily by translating and aligning in silico both coding RNA sequences.

> the way it was optimized differs (not by much but it’s different)

I’m assuming that you’re referring to the codon optimization step that the RNA sequences underwent. While both coding sequences were optimized differently, this has no effect on the final protein product.


Does this mean you can mix the two vaccines - ie. take two shots of moderna, and a later in the year a booster shot of (updated) Pfizer/BnT?

So far I haven’t seen conclusive information about mixing the vaccines, but I think that will be the reality for booster shots late this year/early next year in the UK.


My understanding is that the reason it was required to have the same first and second dose was to make it easier tracing if there was a problem with a particular vaccine and to get the efficacy numbers manufacturers were promising.

From what I heard, in normal circumstances is even recommend to give a booster vaccine shot from a different manufacturer.


While the spike protein is the same, there are differences in the overall formulation and delivery system. An additional booster shot from a different mRNA vaccine should be safe, but still needs to be evaluated. I wouldn’t be surprised if trials are already underway.


I remember reading they had a different something on the scale of ten in the recipe though.


here. do the diff yourself:

https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV...

I’m not gonna go into how the virus was sequenced or what the process to generate the vaccine was, but in this case, I believe your claim of being 100% identical is wrong.


Please read carefully my previous post. Protein sequence != RNA sequence.

I already stated that both coding RNA sequences are different. It is their product, the protein sequence, that is 100% identical in both sequence and structure. The protein that, as you mentioned, is presented as an antigen to the immune system.

If you don’t believe me, and since you already found the FASTA mRNA sequence (or, more specifically, its cDNA equivalent) for both vaccines, you can translate[1] each spike protein RNA section and then align[2] both translated protein sequences.

This is what you get:

  #=======================================
  #
  # Aligned_sequences: 2
  # 1: Pfizer
  # 2: Moderna
  # Matrix: EBLOSUM62
  # Gap_penalty: 10.0
  # Extend_penalty: 0.5
  #
  # Length: 1273
  # Identity:    1273/1273 (100.0%)
  # Similarity:  1273/1273 (100.0%)
  # Gaps:           0/1273 ( 0.0%)
  # Score: 6727.0
  # 
  #
  #=======================================
  
  Pfizer             1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS     50
                       ||||||||||||||||||||||||||||||||||||||||||||||||||
  Moderna            1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS     50
  
  Pfizer            51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI    100
                       ||||||||||||||||||||||||||||||||||||||||||||||||||
  Moderna           51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI    100
  
  ...
  
  Pfizer          1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC   1250
                       ||||||||||||||||||||||||||||||||||||||||||||||||||
  Moderna         1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC   1250
  
  Pfizer          1251 GSCCKFDEDDSEPVLKGVKLHYT   1273
                       |||||||||||||||||||||||
  Moderna         1251 GSCCKFDEDDSEPVLKGVKLHYT   1273

[1]: https://web.expasy.org/translate/

[2]: https://www.ebi.ac.uk/Tools/psa/emboss_needle/


okay. so the vaccine itself is different, but the end result spike protein is the same. I assumed that the spike proteins would look similar (99.5%+) and was actually expecting differences in the “area that holds the protein together at the base where it would normally bind to the useful virus payload”. i guess i was wrong


The overall mRNA is different due to different signal peptides, untranslated regions (UTR), etc. But the mRNA sequence that encodes the spike protein is identical, and presumably that is what would give resistance to variants.


A nitpick: signal peptides are also the same.


It it a Biontech vaccine. Pfizer is only the manufacturer. After all, you also do not call the MacBook a Foxconn Laptop.


In Germany, almost everyone refers to it as the Biontech vaccine. For obvious reasons. I would even go so far as to say that most people here don't realize it's the same as the "Pfizer vaccine". (On the other hand, the Moderna vaccine is referred to as the "Moderna vaccine".)


In Germany BioNTech also involved in the production.. so it is also fair to call it as that..

But I'm a tad annoyed that they pronounce it "Bion-Tech" rather than "Bio-N-Tech", the latter was the intended pronunciation by the owners, I think.


Pfizer (and Fosun) is also the distributor, ran the trials, and handled much of the public/regulator/media facing communications. As such, the Pfizer branding is not surprising.

Production is a multi-step process involving both Pfizer and BioNTech.

https://en.wikipedia.org/wiki/Pfizer%E2%80%93BioNTech_COVID-...


Likewise, look at how Astra-Zeneca made many missteps, mishandling data, sending out wrong doses in trials. Pfizer did not make these mistakes. The distributing company not only matters, it matters a LOT.


In China we call it Fosun/Biontech and that's fine. I would never call it the Fosun vaccin out of respect for the people who actually made the breakthrough.


In HK most people refer to it as BioNTech these days, despite the government's confusing use of the official name "Comirnaty".

The government description seemingly tries to credit Fosun with its development: "mRNA technology platform - by Fosun Pharma in collaboration with the German drug manufacturer BioNTech" [1]

On the plus side, HK is one of the few places in the world where anyone aged 16 or over can currently get their choice of free vaccine (BioNTech or Sinovac) at a nearby vaccine center in about 20 minutes with a booking delay of a couple of days (for defrosting).

Unfortunately, few seem to want it, with bookings running at about 10k/day despite 40k/day capacity for BioNTech alone.

[1] https://www.covidvaccine.gov.hk/en/vaccine


Good to know. That sounds more reasonable than just Pfizer.


We're past that now. It's known as Pfizer in the official language of too many cities and countries.


Can't we all just hate on the now official name for the vaccine of "Comirnaty"?


Marketing person asked to find a catchy name: "This is literally a Covid vaccine, I'll just grab a handful of scrabble pieces and it'll sell anyway"


The actual INN of "tozinameran" is at least better. Not that INNs really get used for products like this.


No, we are not past that. Just because it is used wrongly it does not mean that it needs to stay that way.


Shit happens. Every tissue in the US is called kleenex even though that is a brand.

Lots of people call all kinds of skewers Doner Kebab even though that's incorrect.

It's speech and sometimes it doesn't fit our nice rules.


> Every tissue in the US is called kleenex even though that is a brand.

The only people who call them that are at least 50. Everyone I know except my grandmother calls them tissues. Things change. Shit happens.


What happens on the internet, stays on the internet.


It is maybe for you but not everywhere, i can see it being referred to as Biontech just as often, if not oftener than Pfizer. Maybe because Germany is our neighboor, but maybe also because it is "more right"


Yeah, I was speaking more to California and the US


"many cities and countries" means California, good to know.


I've been ruined by your extremely effective oratory skill.


I only know it as Biontech-Pfizer vaccine.


"Only the manufacturer"?

You mean the company that scaled up production to hundreds of millions of doses, ran clinical trials in dozens of countries for tens of thousands of patients, put together all the regulatory documentation for dozens of countries, including negotiations with regulators, then developed a worldwide logistics system to get the vaccine where it's needed. And did all that with few stumbles in less than a year.

So yeah, they are "just the manufacturer".


But they re like Fosun, one of several. Ofc it s amazing how Fosun managed to vaccinate a million of us in Hong Kong, shipping ultra cold vaccines from Germany and setting up factories soon in Singapore. But man, the vaccine is made by Biontech and without them fosun would be shipping nothing at all.

As for Pfizer, they do nothing at all for me in Hong Kong, see ?


No, they aren't like Fosun. Fosun took possession of finished product and sent it to people doing the vaccinations. That's it.

Pfizer did: 1) scaled up production to hundreds of millions of doses, 2) ran clinical trials in dozens of countries for tens of thousands of patients, 3) put together all the regulatory documentation for dozens of countries, including negotiations with regulators, 4) then developed a worldwide logistics system to get the vaccine where it's needed, including to local distributors like Fosun.


It's more like calling a Dell an Intel. Intel arguably provided the most important R&D in the heart of the computer. But the manufacturing, testing, distribution, branding, sales, negotiations, regulations, etc is all Dell. So go ahead and call your PC an Intel, but it's not wrong to call it a Dell either.


I get where you're at but if you go to the pharmacist and ask which one they have they're going to call this one the Pfizer one.


Same for the Janssen vaccine (from the Netherlands), which is called Johnson & Johnson vaccine everywhere.


That's because Janssen is a wholly owned subsidiary of J&J.


The better analogy would be Foxconn.


True, thanx


It's also GNU/Linux, but few people call it like that.


That’s why Pfizer is behind the whole waving of intellectual property rights so they don’t have to pay Biontech a dime and why the German government is against the waving of rights.


I'm curious, what country are you in? Pfizer is, in fact, against waving the IP rights. You can read it yourself in this letter from their CEO:

https://www.pfizer.com/news/hot-topics/why_pfizer_opposes_th...

Specifically this section:

Which brings me to the second question. Is the proposed waiver going to improve the supply situation or create more problems? And my answer is categorically the latter.


Until it doesn't? I am far from an expert (so please correct me if I'm wrong), but isn't this like saying "the dam can stop any amount of water" ?


No, a dam fails all at once. What has been seen in mutant strains (if anything different) is somewhat reduced protection.


They're talking only about currently worrying variants, not all future possible ones.


They don't mention the B.1.617 variant.


Sure, but if there are already 5 major "variants of concern" in 1.5 years, why are we declaring a premature victory against the variants?


We aren’t “declaring victory”, premature or otherwise, over anything; the results of research that are important in understanding the current, evolving landscape are being published.


I was referring to the headline, which very much has a "mission accomplished" spin to it:

>Pfizer Covid vaccine protects against worrying coronavirus variants

It reads as: "Don't be worried, Pfizer has the variant problem solved."


> I was referring to the headline, which very much has a "mission accomplished" spin to it

That’s really reading a lot into what is a simple, concise, factual headline. There are a set of currently-worrying variants (about which there had been much public concern about the effectiveness of current vaccines), and the Pfizer vaccine is effective against them.

That headline is very much not a “Mission Accomplished” banner.


Emphasis on "currently" which is my entire point and is conveniently left out of the headline. It's an irresponsible headline for something so serious.


This does not mention the variant in India: B. 1.617. Excuse my language but fuck the author and this article. They went out of their way to list multiple other variant names but left the word "India" and "B. 1.617" out entirely while proclaiming "Pfizer COVID vaccine protects against worrying coronavirus variants". Is there another strain that's more worrying right now or even on the day that this article was published?


Scientist seem to be a lot more worried about B.1.351 than B.1.617. Of course newspapers will always hype up the latest thing that was discovered.


The Pfizer vaccine is not used in India, so there's no data on that yet.




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