This is the one headline I’m constantly afraid of reading... do any HN biotech experts have any comments or feedback? Is this a serious cause for concern?
Please note, that neutralization by antibodies is only one of the many possible ways how our immune system can take action. Antibody recognition is still possible with the found mutant:
"To determine whether 501Y.V2 is still recognized by non-neutralizing antibodies, the binding of polyclonal sera (from Fig.2a) to a recombinant 501Y.V2 RBD+SBD1 protein and an RBD+SBD1 from the original lineage was assessed by ELISA (Fig.2b). These data revealed that binding of polyclonal plasma to 501Y.V2 RBD+SBD1 was only substantially affected in a minority of cases (14 of 44 with ≥five-fold reduction, 32%). Most of the convalescent plasma/serum suffered less than four-fold reductions in total binding activity (as measured by area under the curve), suggesting a considerable non-neutralizing antibody component are still able to bind the 501Y.V2 spike antigen"
This is correct, but just want to add that many may interpret this as a positive sign, it is not necessarily. In many cases, binding antibodies increase cell infectivity. Also, there is some research that indicates the presence of non-neutralizing antibodies without the corresponding neutralizing antibodies and humoral response may be a factor in the development of antibody dependent enhancement. As far as we know, it is the neutralization potency that strongly correlates with disease severity.
"On 7 January 2021 it was reported that Pfizer researchers had found the Pfizer and BioNTech COVID-19 vaccine in tests involving 20 blood assays to be capable of affording protection against one of the 501.V2 variant mutations (N501Y, shared with variant B1.1.7). Further investigation was to be undertaken to ascertain the level of protection involved."
The next section in the article is what's important here:
E484K mutation
The E484K amino acid change, a receptor-binding-domain (RBD) mutation, was reported to be "associated with escape from neutralising antibodies" which could adversely affect the efficacy of spike protein-dependent COVID vaccines.[50][51] The E484K spike mutation was linked to a case of reinfection with the 501.V2 variant of SARS-CoV-2 in Brazil, believed by researchers to be the first such case of reinfection involving this mutation.[29] The possibility of an alteration in antigenicity was referred to as an "escape mutation" from a monoclonal antibody with the capability of neutralising the spike protein variants of SARS-CoV-2.[52][53]
I read that. They're only speculating that this could impact vaccines that rely on the spike protein. They didn't actually test for that.
The links I posted show that testing with current mRNA vaccines against this exact variant are under way. Pfizer's (very small) initial tests results seem positive.
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.
But CAN you safely reformulate vaccines to include this new protein and introduce it widely into the population without knowing if this protein's antigen is already present in the body and might cause severe side effects?
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.
> You have to repeat the full range of clinical trials with each reformulation that targets a new antigen.
Are you sure? I don't think we do this with the seasonal flu vaccine in general. It certainly wasn't a consideration in the CDC pandemic flu response fire drill (sequence antigen -> manufactured vaccine in ~2 weeks) that I got a sideline seat on.
"To determine whether 501Y.V2 is still recognized by non-neutralizing antibodies, the binding of polyclonal sera (from Fig.2a) to a recombinant 501Y.V2 RBD+SBD1 protein and an RBD+SBD1 from the original lineage was assessed by ELISA (Fig.2b). These data revealed that binding of polyclonal plasma to 501Y.V2 RBD+SBD1 was only substantially affected in a minority of cases (14 of 44 with ≥five-fold reduction, 32%). Most of the convalescent plasma/serum suffered less than four-fold reductions in total binding activity (as measured by area under the curve), suggesting a considerable non-neutralizing antibody component are still able to bind the 501Y.V2 spike antigen"