Thread by @michaelmina_lab

Will delaying #COVID19 vaccine doses cause vaccine immune escape?

This nice article misses an extremely important part - that unvaccinated ppl too have so called “partial immunity” while infected.

Escape from immunity isn’t same as from antibiotics

1/x

sciencemag.org/news/2021/01/c…

Unlike antibiotics where resistance happens w partial doses, to be a risk you also must be taking them in first place.

When considering escape from spike protein derived immunity - must consider everyone w/out sterilizing immunity at risk to induce a mutant upon infection.

2/x

Whether no vaccine or a single dose (or two) people create antibodies against the same part of the protein.

If discussing “partial immunity” or low affinity antibodies, must consider that a fully naive person might pose greater risk for escape than a single dose person

3/x

In single dose vaccine, at least you are well on your way to and often able to create a strong secondary response - boost antibodies quickly upon infection. Viral replication will be diminished compared to fully naive person. We saw efficacy rose to ~90% before dose 2.

4/x

This of course has to be balanced by a natural infection eliciting antibodies across many epitopes on the whole virus - which could assist in preventing an escape mutant from getting out.

By the time antibodies arise in 1st infection, the virus is often already in decline

5/x

So it could be that the pressure induced by immunity on the virus is so overwhelmingly driven by innate immune products and not antibodies in a naive person that a 1st infection doesn’t pose a large risk of anti-Spike immune escape.

But this might be wishful thinking.

6/x

We’ve seen numerous variants arise already. At least one & likely others have already developed mutations predictable as immune escape by laboratory applied antibody pressures. This caused worry that “moderate” antibodies in ppl upon infection would breed similar effects

7/x

It could - though variants we have now arose independent of vaccines.

The question is which wins out: the more swift control of the virus after a single even if partial dose, or the viruses propensity to mutate if not immediately neutralized by low affinity antibodies.

8/x

We don’t have a clear answer, but I do think any discussion must keep front and center this idea that every fully unvaccinated person too must go through a period of “partial immunity” while battling an infection.

Also, must consider how population level effects play in

9/x

If a single dose decreases transmission enough aid herd effects (again the evidence we do have shows efficacy against disease rose to 90% in short term pre-dose 2) would this have an outsized benefit to reduce risk of escape mutants?

Possibly!

Should be considered.

10/x

Finally the best thing we can do to prevent rise of escape mutants is to decrease spread as much as possible without vaccines.

Rapid frequent accessible tests to everyone, masks, distancing are all helpful here.

Rapid tests might be the most, We should use them.

11/11