The spike protein targeting antibodies produced by the vaccine do indeed target a wider range of spike mutations than the spike protein antibodies from previous infection. However, vaccines only target spike protein, while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity. This is supported by data from Israel and some recent studies.
> However, vaccines only target spike protein, while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity. This is supported by data from Israel and some recent studies
No, it does not.
The data from Israel only supports the claim that immunity from infection is longer lasting than from the vaccine, which should not have been a surprise to anyone.
It does not support any specific mechanistic explanation.
The vaccines also lack a specific abnormal side effect that the infection may carry: risk of death and hospitalization.
Now with death, one could argue that it does provide much longer lasting immunity....
Seriously though, for most people the severity of infection-derived immunity is preconditioned upon them surviving the disease so this looks like the classic "planes with bullet holes" image?
I was confused about that as well. The article suggests that targeting "other portions of the spike protein" (as immune systems previously infected with COVID do) results in the immune system being _less_ robust against variants of the virus than targeting "places on the RBD" (as immune systems exposed to Moderna's mRNA vaccine do):
> Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.
> These findings suggest that natural immunity and vaccine-generated immunity to SARS-CoV-2 will differ in how they recognize new viral variants. What’s more, antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the RBD.
Anyone with more experience in immunology care to weigh in on why the second paragraph there follows from the first? Naively, one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants, not worse. Why is the article saying the opposite?
That really depends on which vaccine. There are several inactivated virus vaccines such as Sinovac used in other countries which we would expect to produce antibodies for more than just the spike protein. However it's unclear whether those vaccines are more or less effective in practice.
As other commentators have noted, it's quite a leap in logic to use reinfection data to make a mechanistic claim on how natural infection may or may not improve the immune response compared to vaccination.
In addition, the naturally-infected and vaccine populations are not the same. For example, having a bad experience with a natural infection of Covid may cause people to not participate as much in virus-risky behavior. On the other hand, people who seek out vaccinations may have done so for business or personal reasons that make them more prone to expose themselves to the virus. It is also possible that (re)infection for the two groups are not monitored at the same rate. Without controlling for these factors (which your first link does not) you cannot make any judgement about which immunity is stronger from your cited data.
Lastly, your second link and your last link directly contradict each other — the second link claims "Recovered COVID patients don't benefit from vaccine" but your last link says "Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection...." If you're going to cite sources, they should probably have a consistent message :).
> while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity.
That is simply not a statement you can make without supporting evidence.
Your immune systems binds to irrelevant targets all the time. People normally got measles once, but lots of people got it multiple times.
It is entirely possible that your immune system will bind to something that mutates rapidly and have worse response than the vaccine.
As someone who got the Covid19 in Original Flavor(tm), I still went and got the vaccine. I don't want to be one of the unlucky ones whose immune system didn't flag the spike protein for destruction.
There's a critical point I think is getting lost in the shuffle: vaccine immunity may be different from natural immunity, but (1) it does seem to protect against severe cases, (2) precisely because the protection is imperfect, the first infection you get after being vaccinated should train the immune system in a similar way as an unvaccinated infection.
So to me, the real question is, what is your immunity like after you get vaccinated AND then infected? Because that's what is most likely to happen in the long run, as COVID becomes endemic. Everyone's going to get an infection, so does vaccine + infection give you better or worse immunity than no vaccine + infection?
I just learned last week that my COVID antibody count from the vaccine is zero. Since I'm on an immunosuppressing medication that wipes out the B cells in my bloodstream, this isn't really all that surprising to me. I learned about this because I'm in a medical study, and other people in the study who take the same medication also don't produce any COVID antibodies in response to the vaccine.
What's interesting is that I still get side effects from the vaccine, and they seem to be right in line with the side effects that other people generally report. I'm no immunologist, but I've taken an armchair interest in the subject since I've been managing an autoimmune disease (MS) for the past 25 years.
The immune system is an amazingly complex thing with many branches. Different types of cells interact in ways that we have yet to fully understand. In spite of having no B cells (except what's in my bone marrow), my T cell count is solidly in the normal range. And the currently-accepted catalog of types of T cells is enough to make your head swim:
Three types of CD4+ Helper T cells are implicated in MS: Th1, Th17, and Th9. And yet by killing the B cells in my bloodstream, for me that seems to stop these T cells from doing MS-like activity without substantially compromising my body's ability to still fight infections.
What does all this mean for my own risk level from COVID, and in particular the Delta variant? Absolutely no clue. I've gotten my third (booster) shot and will be getting more blood drawn next week for the medical study, which I expect will again result in a zero COVID antibody count.
People on my medication have been shown to have more severe cases of COVID when they contract it. I'm a realist about COVID and realize that some day I'll contract it. The best I can do is make sure I'm otherwise in good shape by eating, sleeping, and exercising right. Another option is to go off my medication, let my B cells recover, and then try another less effective medication for a while. For people in my circumstance, there really are no good answers right now.
I know this is all at best tangential to the subject of this study, but I'm glad this research is getting done, and I hope it will lead to a better understanding of how to protect everyone.
Is it possible that your side effects are a result of your immune system reacting against the delivery mechanism (PEG or adenovirus) of the vaccine? Here's one source suggesting this may occur: https://sanchakblog.wordpress.com/2020/12/06/mrna-vaccines-b...
"I'm a realist about COVID and realize that some day I'll contract it. The best I can do is make sure I'm otherwise in good shape by eating, sleeping, and exercising right...."
My goodness, what a remarkably calm and informed attitude. It's a wonder you're allowed on the internet.
By the way, it is theoretically possible that your immune system knows how to make the antibodies, but isn't right now because of the immunosuppressing medication. One strategy might be to only pause that if you get sick, hoping that your system knows how to make the antibodies, and will do so more quickly because you've been vaccinated. But that's just a hopeful guess, of course.
It will be interesting to see how the immune response develops for previously covid-naive vaccinated people after their first covid infection. Specifically, does their immune system still adapt to new variants?
One of the main arguments of controversial anti-covid vaccine people like Geert vanden Bossche is that the immune response generated by the vaccine may thwart the immune system in generating an effective response to future variants after infection[0].
I don’t have enough insight into the immune system’s intricacies to evaluate whether such claims might be legit, but once variants start to emerge that really evade most of the current vaccine-induced immune response, this question will become increasingly important.
It would be interesting to see the duration of the immunity or resistance across multiple vaccine variants. The latest data from the UK indicates that the AZ vaccine suffers less degradation over time than Pfizer, at least when it comes to the Delta variant which is now the prevalent one in the UK.
Israel has now giving boosters to 30 year olds and older in order to boost the immunity to infection and resistance to severe illness.
My understanding is that it may be due to the difference of time during the two shots. It's possible that 2 weeks between the two shots of Pfizer is too short. We're learning.
CoronaVac vaccine? This is a much less effective vaccine than Pfizer and Moderna (https://en.wikipedia.org/wiki/CoronaVac), so it's not surprising that natural immunity would be superior.
I don't think anyone vaccinated is going to be bothered that they didn't have to risk death by COVID (UK mortality rate of 1.99%) to get superior immunity, even if you factor in J&J/AstraZeneca's clotting risk (UK mortality rate of 0.0019%).
Maybe the antibodies are different because the immune system is being presented with _only_ the spike protein, rather than the whole virus?
From my understanding, the immune system breaks the viral proteins up into pieces and then starts rapidly "evolving" antibodies to target those pieces. The goal being to ultimately produce antibodies that target those pieces, and don't target the learned whitelist of proteins (from your own body). Once it's got that it begins deploying antibody producing cells, and remembers the antibodies for later infections.
What I'm curious about is the stopping criteria the body uses during the evolution stage. It sounds like it's producing an array of antibodies, not just one kind. So the stopping criteria isn't finding one working antibody. Perhaps it's more like, "Produce at least N different antibodies."
If the latter, then the difference between natural and mRNA immunity makes sense to me. If your immune system is working to produce N different antibodies for the whole viral proteome, less of those antibodies will target the spike protein. And thus it will have less resilience to changes in the spike protein. But of course more tolerance to changes in the virus as a whole. Whereas with mRNA the immune system only sees the spike proteins, and since it's still going to make N different antibodies it'll have more tolerance for changes to the spike protein.
What's most interesting to me, assuming any of the above is close to reality, is that mRNA vaccines allow us to give our immune system an inductive bias of some kind. Presumably our immune systems aren't "smart" enough to know what parts of a virus are most conserved, and thus best to target. It just targets all of it blindly. mRNA vaccines used the spike protein because we believe that to be the most conserved proteins. If those change too much the virus either won't work, or will effectively be a different species. So our mRNA vaccines are a way of telling our immune systems to focus their work on the "important" proteins, and thus, we would assume, give us better immunity.
Whether our guess about the spike proteins is correct remains to be seen I suppose.
Solid layman reasoning, just wanted to clear up one slight misconception:
> mRNA vaccines used the spike protein because we believe that to be the most conserved proteins
The spike protein was chosen mostly because it was well known to serve a primary role in the process of infection and subsequent immune response. Ongoing vaccine research is exploring the use of additional proteins, because they have been demonstrated to be a major factor in viral replication and protective immunity. For example, nucleocapsid (N) protein antibodies are induced by natural infection, but not by vaccination using the current solely spike protein focused mRNA vaccine formulations. N protein antibodies likely have a synergistic effect with S protein antibodies, and thus vaccine formulations incorporating both elements may result in more robust protection, especially against variants.
See my other comment on this thread for supporting excerpts and citations from the literature.
It's not "make N antibodies". It's a bunch of cells in parallel creating cells specialized to each create a single random antibody. Cells that create antibodies that don't work don't reproduce (linear decay). Cells that create antibodies that worked reproduce (exponential growth). This process stops when the infection is gone.
For the mRNA vaccines, the antibodies only target the some protein, but on the other hand they all target the spike protein.
Natural immunity products antibodies that could match want part oft the virus.
The amount of protection you get against a new variant is related to how well your existing antibodies match the new virus. With natural immunity it is likely that only some of the antibodies match (and since each antibody exists in random amounts, the matching antibodies may be the ones that you have much less of). With vaccine immunity,all of the antibodies produced will work against the new variant if the spike protein is the same, offering nearly the same immunity to the variant as the original virus (assuming the spike protein doesn't change significantly). We know that the spike protein is significantly less likely to change than other parts of the virus so that's a reasonable assumption.
> In this study, we have shown differences in the specificity of polyclonal serum antibodies acquired by infection versus vaccination with mRNA-1273. The neutralizing activity of vaccine sera is more targeted to the RBD than for convalescent sera, with the majority of vaccine sera losing all detectable neutralization at a 1:25 cutoff after depletion of RBD-directed antibodies. (emphasis mine)
From the conclusion:
> Despite these limitations, our results in conjunction with other recent studies (19) suggest that mRNA vaccines and infection elicit somewhat distinct anti-spike antibody responses. Therefore, it is important to differentiate antibody immunity acquired by different means when assessing the impact of viral evolution. Considerable effort is being expended to identify emerging antigenic variants of SARS-CoV-2 and determine which ones might evade immunity (3, 7, 8, 35). Our findings suggest that the results could vary depending on the source of immunity. Furthermore, carefully characterizing and comparing the specificity of antibody immunity elicited by additional vaccine modalities could provide a basis for determining whether some vaccine responses will be more resistant to viral evolution.
If you are wondering whether you are sufficiently protected by having recovered from COVID, this article provides up to date answers. Get vaccinated. Get a booster if recommended.
Amazing this is getting downvoted when this is absolutely the conclusion of these studies in such a straightforward way. Whether or not you were naturally infected, the vaccines provide another layer of protection which can save lives.
This really is the TL;DR of all the research comparing natural and vaccinated resistance. The vaccine provides significant benefits to both folks who dodged the pandemic and those who were infected. There isn't a rational reason to avoid getting vaccinated.
You are being unfairly downvoted, because what you are saying runs contrary to people's gut feelings.
At this point, we have enough statistics on people getting COVID a second time with or without vaccination, to know that vaccination reduces your odds of re-infection by ~2.3. [1]
Let’s look at what these articles are actually saying.. EMPHASIS is mine below:
“Also, it’s POSSIBLE that mRNA delivery may change the way antigens are presented to the immune system, leading to differences in the antibodies that get produced. A third difference is that natural infection ONLY exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system MAY have an even better chance of seeing it and responding vigorously.”
After so many words, what has really been said? Something is possible. MAYBE injecting into a muscle is more effective for a vigorous response. But, folks, the natural infection ONLY exposes the body to the virus in the respiratory tract! (As opposed to ONLY the muscle? Neither is true.)
But hey. We already know before even writing the article… that natural immunity is ONLY this or that, while vaccines are DIFFERENT and HOPEFULLY and MAYBE will give longer lasting immunity than natural one (never mind that studies mostly show otherwise)
How do they get from vacuous statements to a firm conclusion that everyone should take the vaccine?
> antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein.
I wonder how this might impact the design of future mRNA vaccines. For example, could vaccines target multiple proteins that both are associated with the virus?
I don’t see why not since they already do that, both Pfizer and Moderna already have targeted multiple regions on the spike protein, presumably they also modeled them to optimize for antibody interaction and stability by taking regions that are less likely to mutate without loss of function.
If you reach out the limit of what you can encode in a single mRNA payload you can add additional payloads to a single dose or spread them across multiple doses.
Engineered viral vectors also can do similar things and also have a base pair limit so the solution would be similar.
this is referred to as a polyvalent vaccine, and it is a good thing to do once we understand enough about the antigens in question to incorporate both in one shot. There is nothing of course precluding two different vaccines of differenct valence, and we have been doing this for a short time now, when we combine single jab mRna vaccines, with adenoviral vectored vaccines, there is very slight sequence variation between adV and mRNA vaccines however by strictest interpretation this is a multivalant[bivalant] scenario.
Intramuscular vaccinations are the most important first step and will keep hospitalization down. But intramuscular vaccination for respiratory viruses does not provide long lasting immunity to the surface mucosa tissues of the upper respiratory tract. The IgG antibodies in body serum do seep into the lower lungs and provide robust protection from serious disease, but they do not prevent infections very long in the nose, sinuses, or throat. This is the disparity many studies are now highlighting but failing to acknowledge the cause of.
The required next step is intranasal vaccination to recruit B and T cells to the upper respiratory mucosa and have the B cells produce local IgA antibodies. This would actually stop infections (infections defined from nasal swab testing).
It is up to the NIH and other large organizations in the world to get this messaging out there. There are two types of "breakthrough". There's the fact that intramuscular vaccinations don't protect the upper respiratory mucosa, and then there's the very rare cases when sars-cov-2 actually manages to infect body organs and the lower lungs. They are entirely different things.
The variants currently circulating don't play a huge role in this discrepancy. We'd be seeing the same amount of upper respiratory mucosa infections (not hospitalizations) even if there were no delta and it was just alpha/beta/gamma or even original wuhan sequence sars-cov-2.
ref: https://www.gov.uk/government/publications/long-term-evoluti... page 5, #8. "Whilst we feel that current vaccines are excellent for reducing the risk of hospital admission and disease, we propose that research be focused on vaccines that also induce high and durable levels of mucosal immunity in order to reduce infection of and transmission from vaccinated individuals. This could also reduce the possibility of variant selection in vaccinated individuals."
ref: https://science.sciencemag.org/content/373/6553/397 "the ideal vaccination strategy may use an intramuscular vaccine to elicit a long-lived systemic IgG response and a broad repertoire of central memory B and T cells, followed by an intranasal booster that recruits memory B and T cells to the nasal passages and further guides their differentiation toward mucosal protection, including IgA secretion and tissue-resident memory cells in the respiratory tract."
Why isn't there more of a push for emergency use of intranasal vaccines? Apparently there are some in the testing phase, but I think if they were given as much resources as the mRNA vaccines were we might have already had an intranasal vaccine in use by now. The Israelis have one in testing but it still sounds like it's a long ways off from being deployed on a large scale. The other advantage of an intransal vaccine is that we might be able to convince a portion of the vaccine hesitant to get it.
> The new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection.
This seems like a remarkably specific criteria. Using my naive, computer-science brain, I would think that it's unlikely that a mutation would consist of exactly one change to the RBD amino acid sequence (compared to all of the other possible mutations). What am I missing?
> A third difference is that natural infection only exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system may have an even better chance of seeing it and responding vigorously.
But the respiratrory tract is constantly exposed to the external world, wheras the muscles are typically protected by the skin... Therefore I find this fact counterintuitive.
A marketing person might consider this a way of spinning a known negative into a rhetorical positive.
Unless people are being bitten by Covid-bearing mosquitoes, blood serum antibodies aren't going to be seeing virus earlier than the upper respiratory tract.
With natural infection you get BOTH lymphocytic memory of the disease AND antibodies to the disease. With a vaccine you ONLY get the latter. And it's the lack of that balanced duality that creates the risk of ADE or Antibody Dependent Enhancement which is far more dangerous than getting the disease naturally.
I wonder low likely it is that over the course of a lifetime the vaccinated will end up with both forms of immunity. I assume we’ll be exposed to the virus regularly. Would the natural immunity be weaker if it comes from a second, very mild, infection?
[+] [-] bananabiscuit|4 years ago|reply
https://www.israelnationalnews.com/News/News.aspx/309762
https://www.israelnationalnews.com/News/News.aspx/310963
https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...
[+] [-] oldgradstudent|4 years ago|reply
No, it does not.
The data from Israel only supports the claim that immunity from infection is longer lasting than from the vaccine, which should not have been a surprise to anyone.
It does not support any specific mechanistic explanation.
[+] [-] mindfulplay|4 years ago|reply
Now with death, one could argue that it does provide much longer lasting immunity....
Seriously though, for most people the severity of infection-derived immunity is preconditioned upon them surviving the disease so this looks like the classic "planes with bullet holes" image?
[+] [-] Ajedi32|4 years ago|reply
> Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.
> These findings suggest that natural immunity and vaccine-generated immunity to SARS-CoV-2 will differ in how they recognize new viral variants. What’s more, antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the RBD.
Anyone with more experience in immunology care to weigh in on why the second paragraph there follows from the first? Naively, one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants, not worse. Why is the article saying the opposite?
[+] [-] nradov|4 years ago|reply
[+] [-] tylerhou|4 years ago|reply
In addition, the naturally-infected and vaccine populations are not the same. For example, having a bad experience with a natural infection of Covid may cause people to not participate as much in virus-risky behavior. On the other hand, people who seek out vaccinations may have done so for business or personal reasons that make them more prone to expose themselves to the virus. It is also possible that (re)infection for the two groups are not monitored at the same rate. Without controlling for these factors (which your first link does not) you cannot make any judgement about which immunity is stronger from your cited data.
Lastly, your second link and your last link directly contradict each other — the second link claims "Recovered COVID patients don't benefit from vaccine" but your last link says "Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection...." If you're going to cite sources, they should probably have a consistent message :).
[+] [-] FooBarWidget|4 years ago|reply
Does this mean inacticated vaccines work better against variants?
[+] [-] pier25|4 years ago|reply
[+] [-] bsder|4 years ago|reply
That is simply not a statement you can make without supporting evidence.
Your immune systems binds to irrelevant targets all the time. People normally got measles once, but lots of people got it multiple times.
It is entirely possible that your immune system will bind to something that mutates rapidly and have worse response than the vaccine.
As someone who got the Covid19 in Original Flavor(tm), I still went and got the vaccine. I don't want to be one of the unlucky ones whose immune system didn't flag the spike protein for destruction.
[+] [-] civilized|4 years ago|reply
So to me, the real question is, what is your immunity like after you get vaccinated AND then infected? Because that's what is most likely to happen in the long run, as COVID becomes endemic. Everyone's going to get an infection, so does vaccine + infection give you better or worse immunity than no vaccine + infection?
[+] [-] anonuser123456|4 years ago|reply
Current vaccines are intra muscular and lacks a robust mucosal response while natural infection will provide mucosal immunity as well.
As one can imagine, mucosal immunity is very important in an upper respiratory track disease w.r.t. symptomatic infection and transmission.
[+] [-] brainbrane|4 years ago|reply
What's interesting is that I still get side effects from the vaccine, and they seem to be right in line with the side effects that other people generally report. I'm no immunologist, but I've taken an armchair interest in the subject since I've been managing an autoimmune disease (MS) for the past 25 years.
The immune system is an amazingly complex thing with many branches. Different types of cells interact in ways that we have yet to fully understand. In spite of having no B cells (except what's in my bone marrow), my T cell count is solidly in the normal range. And the currently-accepted catalog of types of T cells is enough to make your head swim:
https://en.wikipedia.org/wiki/T_cell#Types_of_T_cell
Three types of CD4+ Helper T cells are implicated in MS: Th1, Th17, and Th9. And yet by killing the B cells in my bloodstream, for me that seems to stop these T cells from doing MS-like activity without substantially compromising my body's ability to still fight infections.
What does all this mean for my own risk level from COVID, and in particular the Delta variant? Absolutely no clue. I've gotten my third (booster) shot and will be getting more blood drawn next week for the medical study, which I expect will again result in a zero COVID antibody count.
People on my medication have been shown to have more severe cases of COVID when they contract it. I'm a realist about COVID and realize that some day I'll contract it. The best I can do is make sure I'm otherwise in good shape by eating, sleeping, and exercising right. Another option is to go off my medication, let my B cells recover, and then try another less effective medication for a while. For people in my circumstance, there really are no good answers right now.
I know this is all at best tangential to the subject of this study, but I'm glad this research is getting done, and I hope it will lead to a better understanding of how to protect everyone.
[+] [-] dimgl|4 years ago|reply
What side effects? How can you know this is coming from the vaccine?
> I've been managing an autoimmune disease (MS) for the past 25 years.
Wouldn't it be more likely that this [multiple sclerosis] is the cause of your symptoms?
[+] [-] AndrewBissell|4 years ago|reply
[+] [-] faeyanpiraat|4 years ago|reply
[+] [-] rossdavidh|4 years ago|reply
My goodness, what a remarkably calm and informed attitude. It's a wonder you're allowed on the internet.
By the way, it is theoretically possible that your immune system knows how to make the antibodies, but isn't right now because of the immunosuppressing medication. One strategy might be to only pause that if you get sick, hoping that your system knows how to make the antibodies, and will do so more quickly because you've been vaccinated. But that's just a hopeful guess, of course.
[+] [-] hybrid_cluster|4 years ago|reply
One of the main arguments of controversial anti-covid vaccine people like Geert vanden Bossche is that the immune response generated by the vaccine may thwart the immune system in generating an effective response to future variants after infection[0].
I don’t have enough insight into the immune system’s intricacies to evaluate whether such claims might be legit, but once variants start to emerge that really evade most of the current vaccine-induced immune response, this question will become increasingly important.
[0] https://www.geertvandenbossche.org/post/not-covid-19-vaccine...
[+] [-] dogma1138|4 years ago|reply
Israel has now giving boosters to 30 year olds and older in order to boost the immunity to infection and resistance to severe illness.
[+] [-] shin_lao|4 years ago|reply
[+] [-] arisAlexis|4 years ago|reply
[+] [-] bobbytit|4 years ago|reply
[+] [-] jiocrag|4 years ago|reply
[+] [-] derkster|4 years ago|reply
[+] [-] fpgaminer|4 years ago|reply
Maybe the antibodies are different because the immune system is being presented with _only_ the spike protein, rather than the whole virus?
From my understanding, the immune system breaks the viral proteins up into pieces and then starts rapidly "evolving" antibodies to target those pieces. The goal being to ultimately produce antibodies that target those pieces, and don't target the learned whitelist of proteins (from your own body). Once it's got that it begins deploying antibody producing cells, and remembers the antibodies for later infections.
What I'm curious about is the stopping criteria the body uses during the evolution stage. It sounds like it's producing an array of antibodies, not just one kind. So the stopping criteria isn't finding one working antibody. Perhaps it's more like, "Produce at least N different antibodies."
If the latter, then the difference between natural and mRNA immunity makes sense to me. If your immune system is working to produce N different antibodies for the whole viral proteome, less of those antibodies will target the spike protein. And thus it will have less resilience to changes in the spike protein. But of course more tolerance to changes in the virus as a whole. Whereas with mRNA the immune system only sees the spike proteins, and since it's still going to make N different antibodies it'll have more tolerance for changes to the spike protein.
What's most interesting to me, assuming any of the above is close to reality, is that mRNA vaccines allow us to give our immune system an inductive bias of some kind. Presumably our immune systems aren't "smart" enough to know what parts of a virus are most conserved, and thus best to target. It just targets all of it blindly. mRNA vaccines used the spike protein because we believe that to be the most conserved proteins. If those change too much the virus either won't work, or will effectively be a different species. So our mRNA vaccines are a way of telling our immune systems to focus their work on the "important" proteins, and thus, we would assume, give us better immunity.
Whether our guess about the spike proteins is correct remains to be seen I suppose.
[+] [-] criticaltinker|4 years ago|reply
> mRNA vaccines used the spike protein because we believe that to be the most conserved proteins
The spike protein was chosen mostly because it was well known to serve a primary role in the process of infection and subsequent immune response. Ongoing vaccine research is exploring the use of additional proteins, because they have been demonstrated to be a major factor in viral replication and protective immunity. For example, nucleocapsid (N) protein antibodies are induced by natural infection, but not by vaccination using the current solely spike protein focused mRNA vaccine formulations. N protein antibodies likely have a synergistic effect with S protein antibodies, and thus vaccine formulations incorporating both elements may result in more robust protection, especially against variants.
See my other comment on this thread for supporting excerpts and citations from the literature.
[1] https://news.ycombinator.com/item?id=28320340
[+] [-] IX-103|4 years ago|reply
For the mRNA vaccines, the antibodies only target the some protein, but on the other hand they all target the spike protein. Natural immunity products antibodies that could match want part oft the virus.
The amount of protection you get against a new variant is related to how well your existing antibodies match the new virus. With natural immunity it is likely that only some of the antibodies match (and since each antibody exists in random amounts, the matching antibodies may be the ones that you have much less of). With vaccine immunity,all of the antibodies produced will work against the new variant if the spike protein is the same, offering nearly the same immunity to the variant as the original virus (assuming the spike protein doesn't change significantly). We know that the spike protein is significantly less likely to change than other parts of the virus so that's a reasonable assumption.
[+] [-] nanis|4 years ago|reply
From the discussion section:
> In this study, we have shown differences in the specificity of polyclonal serum antibodies acquired by infection versus vaccination with mRNA-1273. The neutralizing activity of vaccine sera is more targeted to the RBD than for convalescent sera, with the majority of vaccine sera losing all detectable neutralization at a 1:25 cutoff after depletion of RBD-directed antibodies. (emphasis mine)
From the conclusion:
> Despite these limitations, our results in conjunction with other recent studies (19) suggest that mRNA vaccines and infection elicit somewhat distinct anti-spike antibody responses. Therefore, it is important to differentiate antibody immunity acquired by different means when assessing the impact of viral evolution. Considerable effort is being expended to identify emerging antigenic variants of SARS-CoV-2 and determine which ones might evade immunity (3, 7, 8, 35). Our findings suggest that the results could vary depending on the source of immunity. Furthermore, carefully characterizing and comparing the specificity of antibody immunity elicited by additional vaccine modalities could provide a basis for determining whether some vaccine responses will be more resistant to viral evolution.
[+] [-] Zigurd|4 years ago|reply
[+] [-] bryan0|4 years ago|reply
[+] [-] munk-a|4 years ago|reply
[+] [-] corona-research|4 years ago|reply
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[+] [-] rubyist5eva|4 years ago|reply
[+] [-] mlindner|4 years ago|reply
[+] [-] vkou|4 years ago|reply
At this point, we have enough statistics on people getting COVID a second time with or without vaccination, to know that vaccination reduces your odds of re-infection by ~2.3. [1]
[1] https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm
[+] [-] EGreg|4 years ago|reply
“Also, it’s POSSIBLE that mRNA delivery may change the way antigens are presented to the immune system, leading to differences in the antibodies that get produced. A third difference is that natural infection ONLY exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system MAY have an even better chance of seeing it and responding vigorously.”
After so many words, what has really been said? Something is possible. MAYBE injecting into a muscle is more effective for a vigorous response. But, folks, the natural infection ONLY exposes the body to the virus in the respiratory tract! (As opposed to ONLY the muscle? Neither is true.)
But hey. We already know before even writing the article… that natural immunity is ONLY this or that, while vaccines are DIFFERENT and HOPEFULLY and MAYBE will give longer lasting immunity than natural one (never mind that studies mostly show otherwise)
How do they get from vacuous statements to a firm conclusion that everyone should take the vaccine?
[+] [-] mabbo|4 years ago|reply
I wonder how this might impact the design of future mRNA vaccines. For example, could vaccines target multiple proteins that both are associated with the virus?
[+] [-] dogma1138|4 years ago|reply
If you reach out the limit of what you can encode in a single mRNA payload you can add additional payloads to a single dose or spread them across multiple doses.
Engineered viral vectors also can do similar things and also have a base pair limit so the solution would be similar.
[+] [-] lax4ever|4 years ago|reply
[+] [-] rolph|4 years ago|reply
[+] [-] superkuh|4 years ago|reply
The required next step is intranasal vaccination to recruit B and T cells to the upper respiratory mucosa and have the B cells produce local IgA antibodies. This would actually stop infections (infections defined from nasal swab testing).
It is up to the NIH and other large organizations in the world to get this messaging out there. There are two types of "breakthrough". There's the fact that intramuscular vaccinations don't protect the upper respiratory mucosa, and then there's the very rare cases when sars-cov-2 actually manages to infect body organs and the lower lungs. They are entirely different things.
The variants currently circulating don't play a huge role in this discrepancy. We'd be seeing the same amount of upper respiratory mucosa infections (not hospitalizations) even if there were no delta and it was just alpha/beta/gamma or even original wuhan sequence sars-cov-2.
ref: https://www.gov.uk/government/publications/long-term-evoluti... page 5, #8. "Whilst we feel that current vaccines are excellent for reducing the risk of hospital admission and disease, we propose that research be focused on vaccines that also induce high and durable levels of mucosal immunity in order to reduce infection of and transmission from vaccinated individuals. This could also reduce the possibility of variant selection in vaccinated individuals."
ref: https://science.sciencemag.org/content/373/6553/397 "the ideal vaccination strategy may use an intramuscular vaccine to elicit a long-lived systemic IgG response and a broad repertoire of central memory B and T cells, followed by an intranasal booster that recruits memory B and T cells to the nasal passages and further guides their differentiation toward mucosal protection, including IgA secretion and tissue-resident memory cells in the respiratory tract."
ref: https://www.nature.com/articles/s41577-021-00550-x
[+] [-] UncleOxidant|4 years ago|reply
[+] [-] mactitan|4 years ago|reply
It seems that the new data invalidates that conclusion?
[+] [-] fouric|4 years ago|reply
This seems like a remarkably specific criteria. Using my naive, computer-science brain, I would think that it's unlikely that a mutation would consist of exactly one change to the RBD amino acid sequence (compared to all of the other possible mutations). What am I missing?
[+] [-] bsedlm|4 years ago|reply
But the respiratrory tract is constantly exposed to the external world, wheras the muscles are typically protected by the skin... Therefore I find this fact counterintuitive.
[+] [-] walterbell|4 years ago|reply
Unless people are being bitten by Covid-bearing mosquitoes, blood serum antibodies aren't going to be seeing virus earlier than the upper respiratory tract.
[+] [-] xyzzy21|4 years ago|reply
With natural infection you get BOTH lymphocytic memory of the disease AND antibodies to the disease. With a vaccine you ONLY get the latter. And it's the lack of that balanced duality that creates the risk of ADE or Antibody Dependent Enhancement which is far more dangerous than getting the disease naturally.
[+] [-] dabbledash|4 years ago|reply
[+] [-] unknown|4 years ago|reply
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[+] [-] chaircher|4 years ago|reply