A potential problem for vaccines and new variants of the SARS-CoV-2

I would like to introduce here the concept of OAS - Original Antigenic Sin - and its relationship to exposure to subsequent, mutated strains of a virus to which someone was previously immune, by natural infection or vaccination.

Read this article, which is about the influenza virus, but the principles are the same:

https://www.jimmunol.org/content/202/2/335

The concerning issue here is this: sometimes, due to immunological memory, a subsequent reaction to an updated vaccine may not result in the intended protection against a new variant. This is because the B cells will tend to produce imbalanced sets of antibodies.

Say, natural infection has produced neutralizing antibodies against the S protein, and binding antibodies (which are not neutralizing and not as effective) against other viral proteins such as the N (nucleocapside) protein or the M (membrane) protein or the E (envelop) protein.

Say, a whole inactivated virus vaccine (like the CoronaVac from Chinese maker Sinovac) has produced the same antibodies above.

Say, an mRNA vaccine has only produced antibodies against the S protein, but to three different sites of it, one being essential to the S protein's ability to bind to the ACE2 receptor and infect the human cell, and the other two not as essential.

OK, say that later, then, the person gets infected with a new variant or gets injected with an updated vaccine.

B cell memory may still try to make the old antibodies. It's the "Original Antigenic Sin." These antibodies will be futile if the new variant has mutations precisely in the sites to which neutralizing antibodies previously attached.

Those sites being absent or altered due to mutations, the B cells will tend to over-produce the ineffective antibodies and be too busy to jump start the production of antibodies against the mutated sites or the mutated proteins produced by the new mRNA vaccine.

This means, a person inoculated for the first time with an updated vaccine may develop good immunity against the new variant, but a person who has already received the vaccine and is getting a booster updated shot, may not develop as robust an antibody reaction to the new variant.

Let's propose an analogy. We have a space shuttle (the virus) trying to dock to the International Space Station (the human cell). The ISS has a port (ACE2) that is of a certain size and shape, to which the space shuttle docking port (S protein) will attach.

Say, you want to prevent the docking and you throw some magnets at the space shuttle port, they bind to it, and get in the way so that the space shuttle can't dock to the ISS (these are neutralizing antibodies). Say, you also have magnets that target the walls of the space shuttle. Those attach to the walls but don't prevent the space shuttle from docking (those are binding antibodies).

Now, say that you change the materials of the space shuttle port, hard plastic instead of metal. Magnets don't attach there any longer.

You throw magnets at the port, they don't attach. The shuttle keeps coming. You then increase your throwing of other magnets at the walls. Someone gives you a footprint to make some suction cups that attach to plastic. But you're too busy throwing magnets at the walls so you don't really stop to make the suction cups. Your attack at the space shuttle is inefficient and the shuttle achieves the docking.

Say that you never learned to throw magnets at the metal port of the space shuttle in the first place (previously unvaccinated person), so you're not busy making the wrong kind of defense, therefore when you're given a template for suction cups (the updated vaccine), you jump into making those and you throw them at the shuttle, they attach to the port, and prevent the docking.

Get it?

Maybe getting vaccinated against the ancestral strains, will prevent an efficient response if you're given an updated vaccine against newer, mutated strains.

How certain is this to happen? Not certain. It's very hard to predict this kind of thing. The current vaccines produce what we call a polyclonal response so they do target several regions of the spike protein and may continue to provide protection. I'm just saying, there is a possibility that this virus, if it continues to mutate, will create problems for a percentage of the population, including those who are receiving the current vaccines.

Does it justify waiting for updated shots and refusing the current ones?

No. For now, we believe that the Pfizer shot, for example, remains effective against all variants; the ancestral one, plus the B.1.1.7, the B.1.351., and even the P.1 (recent studies suggest it). Waiting for six months for updated vaccines would be dangerous; one could get infected with the existing variants at some point within these 6 months and get into serious trouble. The existing vaccines, while very good against the ancestral strain and the B.1.1.7, at least offer some protection against the B.1.3551 and the P.1. So, take it, as soon as possible.

But is it possible that with more mutations, in the future you'll be less protected even if you take booster updated shots? Yes, there is a possibility, which is not certain and is hard to quantify or predict.

This is to say, it is very possible, and even likely, that this virus will stay with us forever, with periodic mutations, and we'll have vaccines that will be only partially effective, much like what happens with the influenza virus.

@557 @Quantum Nerd care to comment?

 

I’m going to read all that again and ponder, but @Sallyally, @Quantum Nerd, and I touched briefly on this subject back when T cell cross reactivity was discovered to be a factor with cold coronaviruses and SARS-CoV-2.

I can’t find the thread right off but will look again later. Maybe the others involved remember where to look....

 

Long way of saying the vaccine is useful only for the variants put into it. Shocking, simply shocking.

 

Well, it seems like the point flew above your head. It's not that.
It's this:
Subject A got the ancestral shot, then the updated shot.
Subject B got only the updated shot.
Even though both subject A and B got the same updated shot against the new variant, and even though subject A got more shots, paradoxically subject B got better protection than subject A.
Got it now?
What is shocking is that despite this very clear phrase, you didn't get it:
"Maybe getting vaccinated against the ancestral strains, will prevent an efficient response if you're given an updated vaccine against newer, mutated strains."

 

A long way to describe small details of The Emperor's New Clothes.

 

@CenterField,

I guess after reading your link again and following up on the questions it raises, that’s about all I’ve got—more questions!

It kind of looks to me like it depends a lot on how “damped down” we can get infection rates. It appears with the successful Covid vaccines today we should be able to get annual infection rates much lower than historical influenza infection rates. In that case, coupled with Coronaviruses inherent mutation frequency being substantially lower than influenza viruses (a combination of proofreading ability during replication and total genomic size), we should see a lot less antigenic drift with SARS-CoV-2 compared to influenza. I see that as limiting the possible negative effects of original antigenic sin (OAS) and possibly allowing for more of the “boostering” effects of OAS with few revaccinations for strains with very little meaningful antigenic drift. (I’m still hopeful vaccination for new strains won’t be common).

To me the big wild card is recombination and resultant antigenic shift. Coronaviruses love recombination—even common cold Coronaviruses like HCoV-HKU1 are documented to be prone to recombination. There is a genotype C strain that is the result of a recombination event of strains A and B.

So if a recommendation event happened with SARS-CoV-2 and a cold coronavirus, could OAS be a problem since kids get a lot of colds at a very young age?

Just recently a recombination event involving two existing strains of SARS-CoV-2 was discovered. We don’t know if it only exists in the lab or if it is in the open yet.

https://www.newscientist.com/articl...ants-have-merged-heres-what-you-need-to-know/

So what concerns me more than antigenic drift contributing to OAS is recombinant shift. I don’t know how to compare the odds of OAS with SARS-CoV-2 to influenza because of this even though influenza A does give us recombinants.

By the way, digging into this I discovered the H1N1 virus responsible for the Spanish Flu was a result of direct transmission from animal to human but the H1N1 virus responsible for the 2009 epidemic was the result of a recombination event. Even though they ended up being very similar genetically, one was a result of mutation, the other a result of recombination. I did not know that!

So I guess that’s about all I’ve got. Just my opinion that yes, OAS may cause negative effects going forward. But if it does I think it will be a result of recombination, not antigenic drift as we are seeing in the identified variants today. I think we will see very few point mutation caused variants once we get everyone vaccinated who wants vaccinated.

Fascinating subject, thanks for bringing it up. Here’s the thread I couldn’t find. Not much to it, just acknowledging OAS and ADE could be a factor.
http://www.politicalforum.com/index.php?posts/1071889658/

 

Yes, @557 it looks like @Sallyally had already highlighted OAS.
http://www.politicalforum.com/index...lot-more-than-thought.575750/#post-1071890697

I think that what will happen is that vaccine protection won't ever be complete (it never is, for viruses subject to significant antigenic drift), the virus won't ever be eradicated but will instead become endemic, and we'll need yearly updated shots. Then, some people will get more serious disease through OAS and ADE, and some deaths will continue to occur. Nothing as bad as the 2020-2021 pandemic, as far as the SARS-CoV-2 is concerned.

Until Mother Nature throws us an even nastier bug. It's her way to try and treat the disease, that is, how we humans infect the planet.

These viruses are the antibiotic. The pathogen is humans. Mother Nature eventually will heal herself and kill us all, if we don't die by collective suicide before (such as a nuclear WWIII).