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expert reaction to two NEJM Correspondence articles on in vitro studies of the Pfizer-BioNTech and Moderna vaccines and different variants/mutations including mutations on the South Africa variant

Two letters have been published in the New England Journal of Medicine (NEJM) on the neutralising ability of Pfizer-BioNTech and Moderna COVID-19 vaccine-elicited serum against different SARS-CoV-2 variants/mutations.


Prof Eleanor Riley, Professor of Immunology and Infectious Disease, University of Edinburgh, said:

“This paper extends previous reports of the effect of mutations in the SARS-CoV-2 spike protein on the ability of serum from individuals immunised with either the Pfizer/BioNtech BNT162b2 or the Moderna mRNA-1273 vaccines to neutralise variant viruses. In both studies, the various mutations present in the so-called South African variant (B.1.351) were examined in different combinations. In all cases, including a virus that contains all the B.1.351 mutations, the effective neutralising antibody concentration was significantly reduced.  However, all sera were able to effectively neutralise all viruses.

“These data support the emerging clinical surveillance data suggesting that the BNT162b2 vaccine provides protection against all the variants tested so far; surveillance data for the mRNA-1273 are awaited.  However, there is a theoretical risk that the duration of protection may be reduced. Antibody concentrations decline at a constant rate. Therefore, unless antibody concentrations are boosted by re-vaccination or by natural exposure to the virus, they may eventually fall below the critical threshold for neutralisation of variant viruses whilst still being effective against the vaccine strain. We need to keep an eye on this.

“Virus neutralisation is only one of many potential mechanisms of vaccine-induced immunity. There is, as yet, no evidence that the potency of other immune mechanisms (including T cell-mediated immunity) is affected by these mutations. We await data on the efficacy of these other immune mechanisms against virus variants.”


Commenting on the Pfizer-BioNTech paper:

Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“This is an important study, not least because it confirms that the collection of spike protein mutations found in the so-called South African variant can significantly reduce the virus neutralising potential of vaccine induced antibodies.

“But it doesn’t abolish it completely, so we hope that the vaccine will still have some impact on infection and disease severity; not least because antibodies aren’t the only immunity that the Pfizer vaccine generates.  However, it will still be important to measure the clinical impact of vaccines against circulating variants.

“It also shows that understanding the real impact of virus mutations, you need to test them in the genetic context in which they were found; studying the effect of mutations in isolation may not give you the complete picture.”


Prof Lawrence Young, Professor of Molecular Oncology, Warwick Medical School, said:

“Two preliminary reports confirm that the South African variant of SARS-CoV-2 is more resistant to antibodies induced by mRNA vaccines.  These studies used different approaches to determine the ability of antibodies from individuals vaccinated with either the Moderna or the Pfizer/BioNTech vaccines to block virus infection in tissue culture.

“One study used pseudotyped viruses and showed that while antibodies induced by the Moderna vaccine were able to efficiently neutralise spike protein carrying the changes in the UK variant, this effect was reduced by almost 3 fold in variants with the South African spike protein.

“The other study used engineered SARS-CoV-2 viruses with different combinations of spike mutations.  It showed that a virus with the full set of spike changes found in the South African variant was significantly more resistant to neutralisation (approximately weaker by two thirds) by antibodies induced by the Pfizer/BioNTech vaccine as compared to other viruses containing either a limited set of changes or the more common form of the spike protein.

“The implications of these studies for the efficacy of these vaccines against the South African variant remain to be determined.”


Dr Peter English, Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“The Pfizer press release is mercifully clear compared to the two ‘papers’ referred to1,2.  The papers, incidentally, are not peer-reviewed articles, but letters published in a respected journal.

“Both studies used viruses that had been genetically engineered to express variants of the SARS-CoV-2 spike glycoprotein (the bit sticking out of the virus which enables it to latch on to and enter cells to cause Covid-19 infection); and they mixed these viruses with serum (blood with the cells removed, so it contains the patient’s antibodies but no blood cells) from patients who had been vaccinated with the Pfizer-BioNtech1 or Moderna2 vaccines.  When you do this you can see if the antibodies in the patients’ serum will bind with the antigen (the  SARS-CoV-2 glycoprotein); and if they are ‘neutralising’ (they would prevent the virus from infecting cells of somebody infected with it).  The tests give a quantitative assessment of the amount of neutralising antibody against the specific antigens used.

“Both papers found that the serum of patients who had been vaccinated contained neutralising antibody for all of the antigens tested – including the South African B.1.351 variant.  The quantity of such antibodies was, however, lower, against the South African variant than it was against other variants.

“This adds a little to the information we have; but we must remember that these are ‘in vitro’ findings.  They are only what happens when you mix serum and antigens in the laboratory; and they only test the quantity of neutralising antibodies.  We know that other aspects of the immune response – including cellular immunity (memory cells, killer T-cells and so on) – are also important in the response to this virus.  And we do not know if a particular level of neutralising antibodies in such laboratory tests below which we have reduced immunity to the virus.

“While these findings might, possibly, suggest that the vaccine will be less effective against the South Africa B.1.351 variant, this remains only a possibility – it is far from proven.

“There seems to be little suggestion that the South Africa variant has a particular competitive advantage over other variants – at least in people who haven’t been vaccinated.  This means that the variant seems unlikely to be a predominant strain in the near future – so, even if it is less effective against the variant, there won’t be many people exposed to the new variant, and the vaccine will continue to be highly effective in the medium term.  I think it relatively unlikely that the B.1.351 variant will become a significant problem, but, if it does, by the time it does so, we will almost certainly have vaccines available which are tailored to and will be highly effective against the variant; and, in people already primed by prior infection or vaccination against other variants, a single dose of this new vaccine is likely to elicit a strong ‘heterogenous’ booster response, providing near-immediate, high-quality protection.”

  1. Liu Y, Liu J, Xia H, Zhang X, Fontes-Garfias CR, Swanson KA, et al. Neutralizing Activity of BNT162b2-Elicited Serum — Preliminary Report. N Engl J Med 2021. (
  2. Wu K, Werner AP, Koch M, Choi A, Narayanan E, Stewart-Jones GBE, et al. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine — Preliminary Report. N Engl J Med 2021. (



Pfizer-BioNTech article:

Pfizer-BioNTech press release:

Moderna article:



All our previous output on this subject can be seen at this weblink:



Declared interests

Prof Eleanor Riley: “No conflicts of interest to declare.”

Prof Jonathan Ball: “Receiving funding to develop a DNA-based COVID vaccine.”

Prof Lawrence Young: “No conflicts.”

Dr Peter English: “No interests to declare.”



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