Friday, January 08, 2021

PrePrint: Neutralization of N501Y Mutant SARS-CoV-2 by BNT162b2 Vaccine-elicited Sera

Credit ACIP/CDC  


Given the steady stream of negative reports surrounding the emergence of COVID variants (B.1.1.7 and 501Y.V2) around the world, the headlines overnight - based on a preprint study - (see Reuters Pfizer/BioNTech vaccine appears effective against mutation in new coronavirus variants -study) heralds welcomed - if incomplete - news. 

The study (see below) - while not yet peer-reviewed, and based on lab tests on blood from vaccine recipients - suggests that the Pfizer-BioNtech vaccine is likely still effective against a key mutation (501Y) that occurs in both of these variants.  

While reassuring news, this was not unexpected. The 501Y mutation - which (in concert with others) appears to increase transmissibility of the virus -  was thought unlikely to affect the effectiveness of the current vaccine.  

The more concerning mutation - E484K - which have recently turned up in variants emerging from both South Africa and South America, has yet to be tested in this way. 

This E484K mutation has previously been linked to reduced antibody recognition, which in turn may decrease immune protection acquired from prior infection or vaccination. You'll find an excellent twitter thread from Bloom Labs on the potential ramifications here.

Even if the current crop of vaccines should prove less effective against this E484K mutation (a hypothesis which has yet to be proven), it is unlikely to render them completely ineffective.

That said, over time it would not be unexpected to see accrued mutations eventually degrade vaccine performance, requiring the development of new formulations down the road. 

With a mutable virus, it's always an escalating shot-in-the-arms race. 

While closer to a reprieve than a full pardon, the following study nonetheless provides us with some badly needed positive news.  Follow the link to read it in its entirety.  
Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera

Xuping Xie, Jing Zou, Camila R. Fontes-Garfias, Hongjie Xia, Kena A. Swanson, Mark Cutler, David Cooper, Vineet D Menachery, Scott D Weaver, Philip R Dormitzer, Pei-Yong Shi


This article is a preprint and has not been certified by peer review [what does this mean?].


Rapidly spreading variants of SARS-CoV-2 that have arisen in the United Kingdom and South Africa share the spike N501Y substitution, which is of particular concern because it is located in the viral receptor binding site for cell entry and increases binding to the receptor (angiotensin converting enzyme 2). We generated isogenic N501 and Y501 SARS-CoV-2. Sera of 20 participants in a previously reported trial of the mRNA-based COVID-19 vaccine BNT162b2 had equivalent neutralizing titers to the N501 and Y501 viruses.


A limitation of this finding is that the Y501 virus does not include the full set of spike mutations found on the rapidly spreading strains in the UK or South Africa.3,4 Nevertheless, preserved neutralization of Y501 virus by BNT162b2-elicited human sera is consistent with preserved neutralization of a panel of 15 pseudoviruses bearing spikes with other mutations found in circulating SARS-CoV-2 strains. 

The ongoing evolution of SARS-CoV-2 necessitates continuous monitoring of the significance of changes for vaccine coverage. This surveillance is accompanied by preparations for the possibility that a future mutation in SARS-CoV-2 might necessitate a vaccine strain change. Such a vaccine update would be facilitated by the flexibility of mRNA-based vaccine technology.