Pfizer Inc. and BioNTech SE  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. The results were published on the preprint server bioRxiv and are available here.

Rapidly spreading variants of SARS-CoV-2 have been reported, initially in the United Kingdom and South Africa. These variants have multiple mutations in their spike or S glycoproteins, which are key targets of virus neutralizing 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.

Emerging Variants

B.1.1.7 lineage (a.k.a. 20B/501Y.V1 Variant of Concern (VOC) 202012/01)

• This variant has a mutation in the receptor binding domain (RBD) of the spike protein at position 501, where amino acid asparagine (N) has been replaced with tyrosine (Y). The shorthand for this mutation is N501Y. This variant also has several other mutations, including:
  • 69/70 deletion: occurred spontaneously many times and likely leads to a conformational change in the spike protein
  • P681H: near the S1/S2 furin cleavage site, a site with high variability in coronaviruses. This mutation has also emerged spontaneously multiple times.
  • ORF8 stop codon (Q27stop): mutation in ORF8, the function of which is unknown.
• This variant is estimated to have first emerged in the UK during September 2020.
• Since December 20, 2020, several countries have reported cases of the B.1.1.7 lineage, including the United States and Canada.
• Preliminary epidemiologic indicators suggest that this variant is associated with increased transmissibility (i.e., more efficient and rapid transmission).
• Currently there is no evidence to suggest that the variant has any impact on the severity of disease or vaccine efficacy.

B.1.351 lineage (a.k.a. 20C/501Y.V2)

• This variant has multiple mutations in the spike protein, including N501Y. Unlike the B.1.1.7 lineage detected in the UK this variant does not contain the deletion at 69/70.
• This variant was first identified in Nelson Mandela Bay, South Africa, in samples dating back to the beginning of October 2020, and cases have since been detected outside of South Africa.
• The variant also was identified in Zambia in late December 2020, at which time it appeared to be the predominant variant in the country.
• Currently there is no evidence to suggest that this variant has any impact on disease severity or vaccine efficacy.

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 neutralized 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 U.K. or South Africa, neutralization of virus with the N501Y mutation by the Pfizer- BioNTech vaccine-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. This indicates that the key N501Y mutation, which is found in the emerging U.K 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.