Multiple covid vaccine doses and immune imprinting

[Aldebaran25]

I have been reading about immune imprinting (also known as original antigenic sin... what a term!) and antibody dependent enhancement in relation to covid vaccinations. Are any of you informed about this aspect of the immune response? These are quite complex mechanisms of the immune system whereby the immune response is sometimes so strongly primed against a particular "original" antigen epitope that it will keep responding with the production of antibodies to that specific epitope even when challenged with a different one. It is know to occur with the 'flu vaccine and for dengue fever vaccination. I read these two articles (below) and have been wondering about multiple covid doses. Any knowledge or opinions ?

So far there is no evidence of this process occurring with covid vaccines but I believe it is still a debated issue. Seems that RNA vaccines (Pfizer and Moderna) may be less likely to induce this.

nature.com/articles/d41586-...

sciencedirect.com/science/a...

[Manouche]

He’s certainly right ! « Hensley warns that just measuring antibody levels does not provide a full picture of a complex immune response »

[EPguy]

I hope to get any 4th vax with the Omicron signal in it, if this vax gets approved. It would seem reasonable that switching is better vs continuing even longer with the same vax , but as they say here, not much info.

There was an early SAfrica study indicating that Omicron infection protects against Delta, but not the reverse, so Omicron immunity via vax could be superior to earlier vaxes, if imprinting allows.

In the 1st reference:

<<the problem could also be circumvented in updated COVID-19 vaccines by removing the shared epitopes>>

I think his idea is if you have immunity to the earlier covids why not leave that out of your next vax and keep the next vax all new to the body.

But as Manouche says, immunity has many layers, and these are working well against the worst omicron outcomes.

[Aldebaran25 in reply to EPguy]

Yes, quite a conundrum at this stage. Of course all of this is because I am wondering whether to go for the fourth dose ( booked for next week) now or later on, like you suggest . Trouble is that I will be travelling soon and although omicron, now dominant, is certainly not as dangerous clinically as delta, I would still not like to get caught when away from home . Going for all out protection seems like a good idea but the doubt remains. The professionals in this do however offer a fourth dose and surely they are much more informed and aware of potential risks than we are, so I guess I should trust their judgement,

[EPguy in reply to Aldebaran25]

The experts have been clear that you should take the vax that is available to you rather wait for the one that isn't.

In the context in US, we don't have a general 4th dose yet. It's likely the trials of the omicron specific mRNA vaxes will be completed by March, and that may coincide with a US 4th dose recommendation. Even if the trials are good, they may not authorize, instead continue with the current ones. But the imprinting issue will be on their minds in this decision I expect.