NEJM correspondence paper looking at the neutralising activity of the Pfizer-BioNTech vaccine against SARS-CoV-2 variants in the lab

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March 9, 2021

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A correspondence paper, published in the New England Journal of Medicine (NEJM), looks at the neutralising activity of Pfizer-BioNTech COVID-19 vaccine-elicited serum against different SARS-CoV-2 variants.

A correspondence paper, published in the New England Journal of Medicine (NEJM), looks at the neutralising activity of Pfizer-BioNTech COVID-19 vaccine-elicited serum against different SARS-CoV-2 variants.


Neutralizing Activity of BNT162b2-Elicited Serum

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This work has not been scrutinised by independent experts, or the story does not contain research data to review (for example an opinion piece). If you are reporting on research that has yet to go through peer-review (eg. conference abstracts and preprints) be aware that the findings can change during the peer review process
This work was reviewed and scrutinised by relevant independent experts.

What our experts say

Context and background


Media briefing

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Expert Comments: 

Dr Julian Tang

This is a short Letter by a US team, based on the viral neutralisation capability of 20 sera obtained from 15 Pfizer vaccine trial participants – which showed similar or better efficacy in neutralising SARS-COV-2 wildtype, South African B.1.351, Brazilian P1 and UK B.1.1.7 variants.

Most notably missing is the US CAL.20C variant – now widespread in the USA and detected in several other countries (UK, Denmark, Israel, Singapore, Australia, New Zealand) – which has a different set of S protein mutations (S13I, W152C, L452R) than the other variants above, where the L452R mutation has the potential to reduce S protein target vaccine efficacy.

The Pfizer mRNA vaccine is showing a remarkable ability to neutralise these various variants – at least in vitro with synthetic recombinant viruses.

Will be useful to see if this translates into real world effectiveness going forwards against these variants.

Dr Peter English

This letter to the New England Journal of Medicine describes in vitro studies, looking at how well antibodies generated in response to the PfizerBioNTech vaccine (referred to by its generic name, “BNT162b2”) neutralise viruses engineered to express variant spike proteins.1

They found that levels of neutralising antibodies (measured as the “geometric mean titre” (GMT)) were generated against all of the variants, although this did vary quantitatively between variants. The GMT was highest against the original variant, and against the more transmissible B.1.1.7 variant first detected in the UK; slightly lower against the P.1 variant first identified in Brazil; and lower still against the B.1351 variant first identified in South Africa.

Reassuringly, while the levels were lower for the P.1 and B.1351 variants, they were still substantial, and likely to indicate that the vaccine will be effective.

The study looked in more detail at the precise mutations (the amino acid substitutions or deletions) that might affect vaccine efficacy, as we seem to have seen convergent evolution, where different lineages develop the same advantageous changes.

The authors remind us that these are laboratory findings, based on serum from only 15 individuals; and that other aspects of the immune response, such as T-cell (“cellular”) immunity are likely to be important in real-world vaccine efficacy; and the vaccine “elicits CD8+ T-cell responses that recognise multiple variants”.

Taken together, these findings indicate that this vaccine is likely to be effective against the variants studied, although precisely how effective they are in the real world will require data on the vaccine’s actual effect in populations, not just in laboratory studies such as this one.

This study looked only at the neutralising antibody levels generated in the serum of people who had received two doses of the Pfizer-BioNTech vaccine. In itself, this study does not provide any evidence about other vaccines. However, we know that other available vaccines use precisely the same antigen – albeit delivered in different ways. Given this, It is highly plausible that other vaccines will have similar efficacies against these variant strains – but we do not know this for certain.”

Is this good quality research?  Are the conclusions backed up by solid data?

Yes, this is good quality laboratory research.

How does this work fit with the existing evidence?

The authors refer to studies looking at eg T-cell responses, and the efficacy of the vaccine in the real world. This study is consistent with other in-vitro studies, and adds to what we know.

What are the implications in the real world?  Is there any overspeculation?

This study adds to what we know about the efficacy of the immune response induced by the Pfizer-BioNTech vaccine. It does not claim that the vaccine will be effective against variant strains in the real world, but it is suggestive that it might be effective – although there is insufficient information from this study alone to speculate about precisely how effective.

  1. Liu Y, Liu J, Xia H, Zhang X, Fontes-Garfias CR, Swanson KA, et al. Neutralizing Activity of BNT162b2-Elicited Serum. N Engl J Med 2021. (


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