[Link] Sarah Constantin on RaDVaC

by Orborde5th Feb 20214 comments

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Covid-19
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A couple of minor quibbles:

  1. The peptides did not "come from in silico studies"; they came from the antibody profiles of real patients, who really had covid, and really recovered from covid (ideally without having a Bad Time during recovery.)  So there's more than just computational reasons to believe they will be useful.
  2. It's questionable to complain that radvac did not have a single "research study using any of the peptides in the RADVAC white paper that found they inhibited SARS-CoV-2 infection in cells, let alone animals or humans", when the pfizer vaccine (which we know works) was designed via the same process a year ago, when we had even less information about effectiveness.

How minor are these quibbles? What's your overall estimate of the probability of the RADVAC vaccine working and how much did it change upon reading Sarah's post?

It looks like her objection is that the RaDVaC folks chose some pretty questionable peptides. Presumably you could simply order some different peptides, but I think you'll run into the following problems:

  • You need to pick peptides that will, in the RaDVaC formulation, wind up folded similarly to their conformation in the live virus. I, personally, have no idea how to do that.
  • You don't really have much evidence of immunogenicity for your new RaDVaC formulation and probably need to measure it again (my understanding is that the RaDVaC designers have done some immunogenicity measures in themselves, so the current formulation has some evidence of immunogenicity).

When it comes to chosing peptides, it seems to me like the issue here is that the ferret study used lipopeptides. They do something where they appended cholesterol, in cell-cell fusion assays. This seems more complicated then the RaDVaC peptides. 

In addition to being more complicated to produce the lipopeptides then the RaDVaC choices, you would additionally need to make sure that the rest of the RaDVaC cocktail works well with lipopeptides.

However the lipopeptides might be more stable so they have some advantages. 

It's worth noting here that the ferret study manages to great results with a single peptide. From reading the study it seems to me like their vaccine might be better then the Oxford vaccine which only prevents 2/3 of the patients from being infectious (it prevents more from developing symptoms) as none of the treated ferrets became infectious. It's possible that you need immunity in the mucosal immune system to not be infectious to other people and a nasal vaccine can give that to you while the injected vaccines don't provide that.

Even if half of the RaDVaC choices don't do anything that might still give you a working vaccine.