| re: E484K 1) it's in the spike protein. I think it's in the area that typically elicits antigen response. That's super bad news. If you look carefully, it's near the cleft of a representative antibody (fig 1a), and the buried surface area is high across the board on (clinically?) sampled antibodies (fig 1e), suggesting its importance. 2) it's a mutation that changes the charge state of one of the amino acid residues. E->K, changes a negative charge to a positive charge, potentially very bad if typically antibodies have a positive surface charge to interact with it, now they will be repelled. Since individual humans make random antibodies, even if there is no charge interaction, K amino acid is bigger than E, and so there is likely a shape interaction that could get disrupted by the "new bump" in the spike. Is it a serious cause for concern? Yeah, almost certainly. The current round of vaccinations will probably be rendered inactive. IMO the fastest way around this is to quickly approve a reformulation of the moderna/pfizer vaccines that encode for the new amino acid, or better yet, a cocktail of both. For the more traditional protein-based vaccines, it could be more challenging, because the gut feeling is that an amino acid change like this could pose more of a risk to the effectiveness of the formulation for delivery of the vaccine (mrna is more "neutral" information medium that typically exerts less of a chemical change to the delivered product when altered). In any case this emergent phenomenon will be certainly challenging to the regulatory landscape around vaccination. disclaimer: I own MRNA stock. |
I think you can't. It's famously difficult to anticipate off-target effects of any novel antigen target. This can't be tested in-vitro. You have to repeat the full range of clinical trials with each reformulation that targets a new antigen.