Pfizer Inc and BioNTech SE have announced results from an in vitro study conducted by Pfizer and the University of Texas Medical Branch (UTMB) that shows the antibodies from people who have received the Pfizer-BioNTech COVID-19 vaccine effectively neutralize SARS-CoV-2 with a key mutation that is also found in two highly transmissible strains.
Rapidly spreading variants of SARS-CoV-2 have been reported, initially in the UK and South Africa. These variants have multiple mutations in their spike or S glycoproteins, which are key targets of virus neutralising antibodies. Though these two rapidly spreading viruses are different, they share the N501Y mutation, which is located in the receptor binding site of the spike protein and results in the virus’s spike protein binding more tightly to its receptor. It has been shown to infect mice more efficiently.1
To determine if sera of people who had received the Pfizer-BioNTech COVID-19 vaccine could neutralize SARS-CoV-2 with the N501Y mutation, a virus with this substitution was generated in UTMB’s laboratory. The sera of 20 participants from the previously reported Phase 3 trial neutralized the virus with the mutation as well as they neutralised virus without the mutation.
While the virus tested in this experiment did not include the full set of spike mutations found on the rapidly spreading strains in the UK or South Africa, neutralisation of virus with the N501Y mutation by the Pfizer- BioNTech vaccine-elicited human sera is consistent with preserved neutralisation of a panel of 15 pseudoviruses bearing spikes with other mutations found in circulating SARS-CoV-2 strains.
This indicates that the key N501Y mutation, which is found in the emerging UK and South Africa variants, does not create resistance to the Pfizer-BioNTech vaccine induced immune responses.
Pfizer, BioNTech, and UTMB are encouraged by these early, in vitro study findings. Further data are needed to monitor the Pfizer-BioNTech COVID-19 vaccine’s effectiveness in preventing COVID-19 caused by new virus variants. If the virus mutates such that an update to the vaccine is required to continue to confer protection against COVID-19, we believe that the flexibility of BioNTech’s proprietary mRNA vaccine platform is well suited to enable an adjustment to the vaccine.
Study details
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, View ORCID ProfileVineet D. Menachery, View ORCID ProfileScott Weaver, View ORCID ProfilePhilip R. Dormitzer, Pei-Yong Shi
Published in bioRxiv on 7 January 2021
Abstract
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.
[link url="https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1"]Full study on bioRxiv (Open access)[/link]