Immunity Generated from Covid-19 Vaccines Differs from an Infection

https://directorsblog.nih.gov/2021/06/22/how-immunity-generated-from-covid-19-vaccines-differs-from-an-infection/

by rolph • 5 years ago

240 228 5 years ago

directorsblog.nih.gov

dogma11383• 5 years ago

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.

shin_lao• 5 years ago

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.

dogma11383• 5 years ago

In the UK Pfizer and AZ both are on 8 weeks protocols and the UK has seen a sharper drop in Pfizer efficacy compared to AZ.

I got Pfizer in the UK, I also suspect to have had it in March (3 days of some coughing and loss of smell), I’m under 40 so no AZ for me.

munk-a8• 5 years ago

In part due to immunity duration concerns and, honestly, in part due to supply issues - Canada ended up going way wide on vaccines - most people ended up with twelve weeks between vaccinations.

graywh• 5 years ago

Pfizer is 3 weeks, Moderna is 4

arisAlexis3• 5 years ago

But the lower efficacy drop of Pfizer is still higher than the less degraded AZ efficacy...

bananabiscuit5• 5 years ago

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.

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...

nradov3• 5 years ago

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.

Gibbon1• 5 years ago

I think on a personal basis all of them are better than nothing. It's like advice about taking the first bus out of town.

staticassertion2• 5 years ago

Are there such vaccines available in the US? It seems like those would make for effective boosters.

Ajedi32• 5 years ago

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?

rolph6• 5 years ago

when you target many epitopes, you are shooting at the 10 inch ring; target one epitope of critical function [put one in center of mass] you are shooting the 2 inch ring.

immune systems dont look at everything at once, they find something that sticks and and over trials sharpen the response until highest efficacy of antibody epitope combination is found.

the vaccine is like a laser guided munition, natural immunity is like carpet cluster bombing; both highly effective but in different modalities.

bena• 5 years ago

The way I read it is that vaccine immunity is engineered towards COVID in general. It'll catch variants because they're still COVID.

Natural immunity knows only of COVID-19 Alpha. But it knows it well. All those nooks and crannies the other variants may not have, the natural antibodies can latch on to.

rcxdude• 5 years ago

I think it's because the other parts of the virus are more likely to change over time, because there's lots of neutral mutations available: changes which don't affect fitness but do affect antibody response. The RBD by contrast is much more constrained: most mutations there result in a virus which can no longer infect cells, so it's much less likely to change (though of course any mutations which increase its effectiveness will be heavily selected for). This I think was one of the main reasons the spike protein was targeted by the mRNA viruses.

criticaltinker5• 5 years ago

Why is the article saying the opposite?

The cited study in OP may have a slightly pro-vaccine bias, potentially because two authors have "the potential to receive a share of IP revenue" on a relevant patent, and because one author consults for Moderna. Regardless, the study presents scientifically accurate findings, but in a few places it tries to stretch those into questionable conclusions. For example, the authors write:

At first glance, the RBD targeting of the vaccine sera neutralization might seem likely to increase susceptibility to viral mutations, but the rest of our results suggest that this MAY not be the case. [4]

So keep that tilt in mind when reading it.

one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants

Yes this is good intuition, here are excerpts from other literature illustrating why targeting a wide variety of SARS-COV-2 proteins can provide better immunity. In fact, this reasoning is why ongoing vaccine research is investigating formulations beyond the current solely spike protein focused vaccines. Notably, one shortcoming of the current mRNA vaccine formulations is that they do not induce nucleocapsid (N) protein antibodies - whereas natural infection does.

The nucleocapsid protein of SARS-CoV-2 has been suggested to be an important target for T cell responses. [1]
Firstly, this protein contains conserved cross-reactive T cell epitopes that are present among different coronaviruses, suggesting that it could be an ideal target for universal coronavirus vaccines. [1]
Secondly, the nucleocapsid protein is among the most abundant structural proteins in the coronavirus lifecycle, which may facilitate early antigen presentation and recognition by T cells. [1]
Previous knowledge on other related coronaviruses and the prompt sequencing of the SARS-CoV-2 genome early in the pandemic allowed to identify the spike (S) and the nucleocapsid (N) structural proteins as major targets of antibodies. [2]
The surface glycoprotein S, which contains the receptor-binding domain (RBD), has a better known function in immunity and is the leading antigen candidate for vaccine development. N is smaller than S, lacks a glycosylation site, and is extensively used in leading serodiagnostics kits due to its abundant expression during infection and early antibody response but its immunological relevance is less established. [2]
N forms ribonucleoprotein complexes during the virion assembly process by binding to the viral RNA genome and packing it into long helical structures. Its main function is to regulate viral RNA transcription during replication, promoting the synthesis of its own proteins while interfering with the metabolism, protein translation, and proliferation of the infected host cell. During the process of infection, N dissociates itself from the genome and is exposed to the host immune system, and its high immunogenicity has also prompted its exploration as vaccine target. [2]
Interestingly, significant protein similarity between SARS-CoV-1, SARS-CoV-2, and other HCoV has been reported for N, including a highly conserved motif in the N-terminal (NT) half of the protein (FYYLGTGP) and relevant immunodominant epitope regions. [2]
Evidence from multiple experimental studies showing that single RBD point mutations can lead to resistance to neutralizing convalescent plasma from multiple donors suggests that specific single mutants may be able to evade spike-targeting vaccinal immunity in many individuals and rapidly lead to spread of vaccine-resistant SARS-CoV-2. [3]

[1] Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2 https://www.cell.com/cell-reports/pdf/S2211-1247(21)01108-6....

[2] Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879156/

[3] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/

[4] Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection https://pubmed.ncbi.nlm.nih.gov/34103407/

randcraw• 5 years ago

Inoculation with an mRNA vaccine provides recognition of few antigena (e.g. RBD). The size of the vaccine dosage and the delay of a month between doses is designed to create a strong recognition of the chosen antigens.

Infection's response to key antigens like RBD is inherently more limited because: 1) immunity creates antibodies and T cells that target a wider range of antigens, and 2) exposure to COVID antigens usually fades after 7-10 days, limiting the immune system's time to build further defenses.

jyounker5• 5 years ago

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?

The RBD is the part of the spike protein that latches onto the cell. Specifically it latches onto the ACE2 receptor. If the RBD changes too much then the virus can no longer infect its target cells (because it can't attach to ACE2 receptors). This means that there are probably strong limits on how much this section of the virus can change.

Because we expect the RBD to change less than other areas, and because the mRNA vaccines recognize more of these possible changes, then we have a reasonable expectation that mRNA based immunity should continue to be effective.

To make a crude analogy, ACE2 is a phillips head screw. The spike protein is a phillips screw driver. The tip of the screw driver is the RDB. Infection elicited antibodies recognize random spots all over the screw driver. mRNA vaccine elicited antibodies recognized spots all over the tip. Eventually you can turn the handle into a shape that won't be recognized, but there are strict limits on how much you can change the tip while still having it function as a philips screw driver. And of the ways that you can change the tip, the mRNA antibodies will match more of them than the naturally acquired ones. At least that's the expectation.

There are still possible ways that the virus might evade; perhaps by making shields for the tip that block portions of the antibody, but this seems like it might be harder than changing the handle's shape.

FooBarWidget• 5 years ago

What about inactivated vaccines such as Sinovac? Does that immune response resemble natural infection?

Does this mean inacticated vaccines work better against variants?

pier25• 5 years ago

Another consequence of this is that, theoretically, the virus could mutate and be unrecognizable by the antibodies produced by the vaccine.

stillbourne• 5 years ago

The same could be said for convalescent immunity too.

BurningFrog• 5 years ago

One reason the vaccines target the spike protein is that it's how the virus breaks into human cells.

It it mutates to a different spike shape, it's very unlikely that it will keep that breakin power.

Or at least that is the assumption :)

trhway• 5 years ago

and given that vaccines target only a segment and pretty much the same segment, such mutation based escape from all of the vaccines at the same time is of very high probability - https://journals.plos.org/plosone/article?id=10.1371/journal... . And the fact that the current vaccines don't prevent delta infection seems to confirm it. Whereis natural immunity targets multitude of the segments (and not only of the spike protein) thus naturally providing much more robust immunity.

We need a vaccine for delta. Unfortunately from MBA perspective it is much more profitable to push the current vaccines down the throat of the populace through forced mandates and hysteric propaganda instead of investing additional billions in the vaccine for the mutated virus.

2 shots don't work, thus the 3rd, "booster", then what? the 4th? It is pretty typical for the medical industrial complex to push to sell more and more product in response to low effect, like that opioid dosage increase.

oldgradstudent2• 5 years ago

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.

lamontcg3• 5 years ago

Honestly I have yet to see any convincing scientific evidence that is free from confounding factors which suggests that there is waning immunity.

And there's reason to believe from HCoV-229E that immunity against coronaviruses is actually durable and that reinfection is due to mutation and immune escape.

https://journals.plos.org/plospathogens/article?id=10.1371/j...

rossdavidh6• 5 years ago

From the last link: "Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant."

Note the "longer lasting and stronger".

criticaltinker5• 5 years ago

It does not support any specific mechanistic explanation.

You're right that the recent pre-print cited by GP - regarding the data out of Israel - does not prove or disprove any specific mechanistic explanation.

However, interpreting GPs comment charitably, that study does support the notion that immunity acquired through natural infection may be more robust to mutations and variants - the mechanisms of which have been articulated in a variety of other literature. See my sibling comment [1] for supporting citations and excerpts.

[1] https://news.ycombinator.com/item?id=28320340

buu700• 5 years ago

which should not have been a surprise to anyone

Why is that? I have no background in immunology so it's mildly surprising to me.

phkahler• 5 years ago

> No, it does not.

But is is acknowledged in the article linked here:

> 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.

It does not follow that vaccination conveys better immunity than previous infection. Only better response to mutations in one area of the spike protein. Nothing else is being claimed in this paper.

geoduck14• 5 years ago

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.

I find that surprising. Why did you expect that? Why should I have expected that?

georgeplusplus• 5 years ago

>>> 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.

Apparently it is a surprise for USA and Europe as the former only recognize infection based immunity for three months and the latter recognizes it for 6 months, while some EU member states recognize vaccine based immunity for 8 months.

please do not make stuff up to fit your narrative.

tylerhou• 5 years ago

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 :).

bananabiscuit5• 5 years ago

That mechanism of action is just what I’ve seen put forth by immunologists commenting on the these kinds of results.

While the author’s opinions on the necessity of vaccines do differ, they do agree on my main point: that empirically, natural immunity is indeed robust and tentatively even better than vaccine acquired immunity.

It looks like getting a vaccine helps boost immunity in all cases, whether you had a previous infection or if you had 2 doses and I would bet even after the booster, each additional shot will continue to provide some marginal benefit. So keep getting jabs, I guess, or you’re killing grandma.

I think at this point throwing in “you should vaccinate (regardless of your individual circumstance)” into your conclusion, even if it’s a complete non-sequitor, is a hedge against losing your job/funding/respect of your equally frightened peers. The COVID research equivalent of the “making the world a better place” SV trope.

bsder• 5 years ago

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.

walterbell7• 5 years ago

People normally got measles once, but lots of people got it multiple times

Is there a good reference for the percentage of people who did?

mindfulplay2• 5 years ago

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?

fspeech3• 5 years ago

Not with inactivated virus. There are vaccines based on that.

__blockcipher__2• 5 years ago

The vaccines also lack a specific abnormal side effect that the infection may carry: risk of death and hospitalization.

This is well-intentioned but false. The vaccines can send you to the hospital (side-effects). It's rare but happens. Similarly, you can be vaccinated, get infected with SARS-2, and end up in the hospital, so it's not even true that they avoid hospitalization from SARS-2 itself completely. (They help a lot with hosp/death from the virus, to be clear)

Zigurd• 5 years ago

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.

vkou2• 5 years ago

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]

[1] https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm

bananabiscuit5• 5 years ago

This is true. But given the already high baseline immunity for previously infected people, the messaging for them should be somewhere closer to “you can get the vaccine if you want” rather than “you must get the vaccine otherwise you are causing the pandemic”.

munk-a8• 5 years ago

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.

bryan0• 5 years ago

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.

mlindner• 5 years ago

There's no reason to get a booster. The only people pushing that are government officials who are running counter to scientific advice.

literallyaduck• 5 years ago

Can you provide sources?

rubyist5eva2• 5 years ago

nah, I'm good

mabbo• 5 years ago

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?

rolph6• 5 years ago

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.

cblconfederate3• 5 years ago

it also generates immunity to the adenoviral vector proteins

dogma11383• 5 years ago

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.

lax4ever• 5 years ago

Looks like they are trying to do something exactly like that: https://news.ycombinator.com/item?id=28319391

anonuser123456• 5 years ago

Antigen targets aside, there is also a difference in the production of antibodies in the mucosal system.

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.

UncleOxidant2• 5 years ago

Yeah, why aren't we putting more effort into getting an intranasal vaccine approved for emergency use? An intranasal vaccine would confer mucosal immunity and might also be more acceptable to the vaccine hesitant. They're talking about 3rd shot boosters, but I'd really like to be able to get an intranasal vaccine as the third booster.

nradov3• 5 years ago

Nasal vaccine trials are underway. We should have preliminary results in a few months.

https://www.medpagetoday.com/special-reports/exclusives/9252...

pettusftw• 5 years ago

IIRC there is an intranasal expected to be approved mid next year. I can't find the source I read that in, so take the timing with a grain of salt. Another source I can't find at the moment mentioned questions about the duration of protection from that method of vaccination as well.

I would guess the push for intramuscular was driven for multiple reasons, the first being ease of development and the second to keep hospitalizations and death at a minimum.

jart5• 5 years ago

I don't think anyone's concerned about IM vs. IN as they are mRNA vs. DNA. The boosters deliver double stranded helix straight to the nucleus like a Windows update. You'd have to pull an Apocalypse Now to roll that back. GM people nobody panics but GM organic food and everyone loses their minds.

superkuh4• 5 years ago

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."

ref: https://www.nature.com/articles/s41577-021-00550-x

UncleOxidant2• 5 years ago

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.

rolph6• 5 years ago

nasal mucosal immunity[IgA] is short term relative to humoral immunity[IgG; IgM]; this however would be a good prophylactic approach, as the nasal vault is a major contributor to transmission mechanisms

Animats• 5 years ago

Here's a good explanation of why.[1] There are several intranasal coronavirus vaccines in test. There's only one approved nasal vaccine now, for anything: FluMist. It's not recommended for people over 50. There have been previous failures. Intranasal vaccines are hard to make work.

Think of the current mRNA vaccines as a minimum viable product. The basic formulation was computed days after the virus was sequenced and they made it to market fast. They do the basic job. Serious side effects are rare. They require two doses and later, boosters. They're a pain to store and ship because of cold requirements. They're hard to manufacture because putting fragile messenger RNA into a liquid carrier envelope requires exotic equipment. They have reduced effectiveness for virus variants.

Expect later-generation products that solve some of those problems.

[1] https://www.pbs.org/newshour/health/scientists-debate-potent...

civilized3• 5 years ago

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?

pajamanaut• 5 years ago

It seems like the article is saying that vaccine immunity is actually more robust that natural immunity though.

flatiron• 5 years ago

For spike proteins. Not for the other targets you get with natural immunity.

civilized3• 5 years ago

Good point, edited to clarify.

Beyond just this study, which doesn't give the whole picture of immunity, I think there is conflicting evidence. Given that vaccine effectiveness seems to be going down in Israel, I think there are legitimate concerns about the robustness of vaccine-based immunity - but the question is always "relative to what?". If it ultimately sets you up similar to or better than natural immunity from an infection (which also wanes, as we get, e.g., colds over and over throughout our lives), that's the best you can hope for.

oldgradstudent2• 5 years ago

If that's the case, then they should retract and work towards understanding why their methodology failed so miserably.

The data from Israel shows an order of magnitude better immunity from prior infection than the vaccine.

arisAlexis3• 5 years ago

And then the question is, should you as a vaccinated healthy person mind getting infected in the sense that it can shield you maybe even more from future variants or is this a dangerous game to play?

nightfly• 5 years ago

I think it's all about timing. Right now in Oregon our hospitals are full. So the less people getting infected right now the better.

maxerickson2• 5 years ago

It's probably still worth trying to reduce the amount of virus in circulation, even if individual risk is low. There's someone in another thread talking about being on immunosuppressants, for example.

I don't think it's a binary condition either, we can do things that are more effective and less costly (like cutting down on large, indoor, adult social gatherings) and not do things that are less effective.

randomopining4• 5 years ago

That's what I've been proposing for a few months. Get the vaccine and then get the delta variant a few weeks later to crush it and then be super immune for future variants that jet off of that one.

beamatronic• 5 years ago

Here's a pragmatic question - do we need large amounts of people who have natural (non-vaccine) antibodies to donate their blood? To put it more crudely, is there a way that everyone at large can benefit from their (unfortunate) suffering?

rossdavidh6• 5 years ago

I know someone who has been donating for exactly this purpose (he's a bar owner, and apparently was told by his doctors that he had an extraordinarily high antibody count). Unfortunately, the results from all of these kinds of treatments thus far has been less than hoped for.

bradydjohnson• 5 years ago

Individuals with a combination of history of COVID and vaccination appear to have exceptionally strong protective immunity that has been described as "bulletproof." As published in Nature [1] and analyzed by JAMA [2], individuals who had been infected (even those with mild disease) and vaccinated had over 50 times more neutralizing antibody activity than those who were unvaccinated. This level of protection was more robust even than that seen in fully vaccinated individuals.

[1] https://www.nature.com/articles/s41586-021-03696-9 [2] https://jamanetwork.com/journals/jama/fullarticle/2782139

civilized3• 5 years ago

It would be interesting to know the order of events in the population studied (vaccination first or infection first?) and whether it seems to matter for the ultimate level of immunity achieved.

nanis• 5 years ago

Full text here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369496/

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.

fouric• 5 years ago

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?

cblconfederate3• 5 years ago

A variant has multiple mutations which they call "single letter changes". It's not meant to say that there will be only one mutation per variant

rolph6• 5 years ago

single letter change is refered to as a point mutation meaning one residue. it is common

there are a number of mutation types and numerous mechanisms.

https://en.wikipedia.org/wiki/Mutation

in the case of point mutations, cosmic ray ablation, and wobbly fit of the replication mechanism lead to data corruption, conflated by error prone replication or error prone proof reading

brainbrane3• 5 years ago

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:

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.

AndrewBissell• 5 years ago

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...

rossdavidh6• 5 years ago

"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.

rossdavidh6• 5 years ago

Just to make sure, the bit about "remarkable calm and informed", was not mean ironically.

dimgl• 5 years ago

What's interesting is that I still get side effects from the vaccine

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?

fshbbdssbbgdd2• 5 years ago

I assume we’re talking about the acute flu-like side effects commonly experienced in the days after getting the vaccine. Presumably this person can tell the difference between those and whatever they’ve had for the previous 25 years.

throw_nbvc1234• 5 years ago

Probably means the typically vaccine side-effects that are similar to getting a cold as your body "fights off" the vaccine and develops immunity.

Johnny5553• 5 years ago

Wouldn't it be more likely that this [multiple sclerosis] is the cause of your symptoms?

More likely than "immunosuppressing medication that wipes out the B cells in my bloodstream"?

faeyanpiraat3• 5 years ago

Which medication are you using?

webinvest• 5 years ago

Maybe one for HIV/AIDS? That disease is an eventual death sentence.

brainbrane3• 5 years ago

Ocrelizumab.

bsedlm• 5 years ago

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.

walterbell7• 5 years ago

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.

hybrid_cluster• 5 years ago

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.

[0] https://www.geertvandenbossche.org/post/not-covid-19-vaccine...

fpgaminer• 5 years ago

A layman's take:

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.

IX-103• 5 years ago

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.

criticaltinker5• 5 years ago

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.

[1] https://news.ycombinator.com/item?id=28320340

dabbledash• 5 years ago

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?

bobbytit4• 5 years ago

This more recent Thai study shows that natural immunity is far superior for all known variants... https://www.news-medical.net/news/20210719/Thai-study-looks-...

jiocrag2• 5 years ago

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.

bobbytit4• 5 years ago

What about the Israeli study then.. http://www.google.com/url?q=https://www.spectator.co.uk/arti...

It found that double pfizer jabbed people were 13 times more likely to be infected than those who had already recovered.

derkster4• 5 years ago

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%).

mactitan• 5 years ago

Informed consent disclosure to vaccine trial subjects of risk of COVID‐19 vaccines worsening clinical disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645850/

It seems that the new data invalidates that conclusion?

nickthemagicman• 5 years ago

Wouldn't this open the door to possible immune diseases in the long term?

With a much wider net for the antibodies to attack, someone with the DNA and matching proteins that are similar to the spike protein would have an increased chance of an autoimmune disease.

EGreg• 5 years ago

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?

chaircher• 5 years ago

I mean yeah but the point is to not get infected in the first place right?

xyzzy21• 5 years ago

Yeah, true that.

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.

Immunity Generated from Covid-19 Vaccines Differs from an Infection

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