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expert reaction to preprint suggesting the Pfizer/BioNTech vaccine might be effective against new variants

A preprint, an unpublished non-peer reviewed study, suggests the Pfizer/BioNTech COVID-19 vaccine might still be effective against the new SARS-CoV-2 variants.

 

Prof Deborah Dunn-Walters, Chair of the British Society for Immunology COVID-19 and Immunology taskforce, and Professor of Immunology at University of Surrey, said:

“Vaccines work by stimulating our immune response, which has an incredible ability to make a highly diverse library of antibodies against the virus. Therefore we would expect a person’s immune response to be diverse enough to cope with some changes to the virus structure. It is reassuring that Pfizer are closely monitoring whether variants of the SARS-CoV-2 virus can escape the immune responses elicited by their COVID-19 vaccine, and that so far there is no evidence that the mutations tested have made any difference to antibody ability. Of course this needs constant monitoring, and the South African variant has a mutation of concern, but even if we did see any differences, the technology used to make the vaccines means they can be changed quite quickly if necessary.”

“A limitation of this study is that the mutation was tested in isolation. Where evidence, such as structural modelling, indicates that mutations could interact with each other to affect the overall antigen structure they should be tested together.” 

 

Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“The authors say “no reduction in neutralization activity against the virus bearing the Y501 spike”.  But looking at figure 1 it does seem to me that there is a reduction of a single dilution in the assay in about a half of all sera tested. The authors have helpfully drawn lines for those sera that did exhibit different inhibition titres between the two variants. How is this figure compatible with the statement? I suspect the issue is that when comparing a single serum or paired sera we generally need a twofold change to be sure so on any one serum a one fold difference would not be taken as being significant. But when looking at multiple sera then a one fold decline in titre in about half of cases and only one increased titres in the remaining does suggest an impact.

“Sometimes you get the appearance of an escape mutant (antigenic shift for influenza) that renders all its daughter viruses resistant to pre-existing immunity.  Often you get a build up over time of small mutations (antigenic drift for influenza) that gradually produce daughters with increasing resistance. It does seem to me that this preprint does suggest a small increase in resistance to vaccine produced antibodies, that even if not sufficient in itself could in combination with other mutants be an important step on the pathway to reduce the efficacy of pre-existing vaccines.

“The other issue is that a recent preprint1  found that the most important mutation giving resistance to immunity following natural infection may be at E484 which is a mutation in the South African variant which of course would not be covered by the preprint by Xie et al. and as far as I can tell by the preprint by Sahin to which Xie refers2 . However, it is not clear to me whether the E484 site is important in immunity with existing vaccines, but this needs to be confirmed.

“So at present the jury is still out on the impact of the South African variant on vaccine efficacy. It is likely that vaccines will still be effective but maybe a little less so unless of course additional variants arise.”

1 https://www.biorxiv.org/content/10.1101/2020.12.31.425021v1

2 https://www.medrxiv.org/content/10.1101/2020.12.09.20245175v1

 

Prof Daniel Altmann, Professor of Immunology, Imperial College London, said:

“This is indeed an important finding to calm any concerns about lack of vaccine coverage for the variants. The protective, neutralising antibody response that blocks spike entry is ‘multi-epitope’ – that is, targeted to several bits – so it was unlikely that protection would be significantly impaired. Neutralisation of the variant looks excellent from this study.”

 

Prof Ravi Gupta, Professor of Microbiology at the University of Cambridge, said:

“The short report, showing a single Spike mutation has little impact against serum from individuals vaccinated with the Pfizer vaccine, is misleading for a number of reasons. Firstly, the mutation selected is only one of 8 in the UK variant, and in fact was not expected to have significant impact alone. Secondly, primary titration curves are not presented so one cannot see how well the experiments worked and what the measurement error was. The number of times the experiments were repeated is not given. This work should be ignored until properly conducted work is made available. The present paper would not pass peer review in its current form.

 

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

“So far, so good. There will be other new mutants and we will need to monitor the situation carefully by repeating this type of study on new variants as they appear. It may be necessary to tweak the vaccine over time.

“To inject a little optimism into the discussion: there is a limit to the number of mutations the virus can accumulate and still be able to bind to the receptor. We probably have enough structural data now to be able to predict which mutations will retain receptor binding but may evade antibodies. So we may be able to get ahead of the virus by preparing vaccine constructs that would cover this eventuality.”

 

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This is good news, mainly because it is not bad news. Had the opposite result been found, that the vaccine did not seem to have efficacy against the variation of the virus studied, that would have been bad and very concerning. So, yes this is good news, but it does not yet give us total confidence that the Pfizer (or other) vaccines will definitely give protection. We need to test this in clinical experience and the data on this should be available in the UK within the next few weeks.

“This lab-based testing is useful but is not the exact variant found in the UK.

“The study, with these limitations, is a good one and, in this case, the lack of peer review is not a major limitation.”

 

Prof Ian Jones, Professor of Virology, University of Reading, said:

“The new data provides important confirmation that the multiple antibodies generated against the S protein by vaccination remain able to inhibit cell entry by variant viruses. This is because while some antibodies may not bind to S proteins with, for example the N501Y mutation, most antibodies still do, and this is sufficient to maintain protection.

“The use of monoclonal antibodies, which bind to only limited regions of S, for therapy may be more susceptible to evasion by variant viruses but that can be assessed in similar ways and different combinations of antibodies used if required. There is no case currently to suppose that ongoing vaccination is not going to be successful.” 

 

Dr Alexander Edwards, Associate Professor in Biomedical Technology, Reading School of Pharmacy, University of Reading, said:

“This is exactly the kind of data that is needed to better understand how any mutation or variant might affect vaccine function. The experiment described takes blood serum from volunteers immunised with the Pfizer-BioNTech vaccine and shows that it has equal ability to block one of the important mutations in the two concerning variant virus forms, as it does to block the original virus.

“This particular data release before peer review is extremely useful as it allows very rapid assessment, and such rapid sharing of essential data must be applauded. However, expect much larger studies using different methods, more samples, and with different vaccines, and that will take longer to run and fully analyse before we can have complete confidence about protection levels. This small preprint only contains a small amount of data. Because there are multiple variants of concern, each with several mutations that could change function, this kind of study will be repeated independently by many different labs for each variant of concern and each important mutation, so we can gain a scientific consensus.

“We will need to see actual protection from new variants in participants in the clinical trials that are still running to be sure the vaccine is equally effective. But even this initial lab data is already extremely encouraging, as it supports what would be expected from the biology of immunity against this type of virus. As explained by molecular virologists: so far relatively small changes in the spike target of vaccines have been spotted, so most of the protection given by the new vaccines will still work fine.”

 

Prof Gary McLean, Professor in Molecular Immunology, London Metropolitan University, said:

“It’s a very short paper, not really even a paper – just some experiments written up into a communication.

“However, they made mutant SARSCoV2 viruses with wild type N501 or the Y501 spike variations and have shown that 20 sera from previously vaccinated people can still neutralise the virus in vitro and in fact is equivalent i.e. both variants were neutralised equally by sera from people immunised with the N501 variant. Sera was obtained 2 and 4 weeks after the standard two dose regimen – presumably separated by 3 weeks as per guidelines (not the UK “let’s give as many the first dose and then eventually get around to the second dose regimen”). This could be critical.

“Its good news, but not surprising.  The limitation is that they did not construct SARS-CoV-2 with the full set of spike mutations in the UK variant and therefore further conclusions cannot be made fully at this stage.”

 

Prof Lawrence S. Young, Virologist at the University of Warwick, said:

“This is very encouraging news, The preprint demonstrates that antibodies from individuals vaccinated with the Pfizer/BioNTech mRNA vaccine is able to block infection (neutralise) with an engineered form of the SARS-CoV-2 virus that contains one of the key mutations in the spike gene (N501Y) found in the UK variant. This mutation is also present in the South African variant. However, for both virus variants there are other changes which might affect infectivity and these have not been examined. This is particularly a concern with the South African variant which has accumulated two additional changes in the key receptor-binding domain of the spike gene. These changes are very likely to influence the infectiousness of this South African variant and may also impact its ability to be blocked by antibodies – particularly the monoclonal antibodies that have already been used as a therapy. It is also worth stressing that the blood (sera) used in this study was taken from individuals who had received the second dose of the vaccine. This highlights the importance of the second dose. These individuals had received the second dose three weeks after the first and the blood for this study was then taken either 2 weeks or 4 weeks after the second dose.”

“It is very important that we examine the immune response in individuals infected with these different virus variants.  This will enable us to determine the nature of the antibody and T cell responses to the UK and South African variants. 

“It is very likely that individuals infected with these variants will generate a protective immune response but the profile and specificity may be slightly different from that observed in previous studies with the original virus. This information will help us to determine the likely effectiveness of current vaccines as well as guide the development of any future vaccines.”

 

Prof Rowland Kao, Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, said:

“Should these results prove robust, it is of course good news that the vaccines we have available are effective. The result for a single vaccine do not of course necessarily translate to the impact on the others available, but there is high probability that others will be effective where the mechanisms of protection are very similar.

“This does not of course mean that in future, new variants which do have a substantial impact on vaccine efficacy won’t evolve. The probability that this occurs will likely increase as we ramp up vaccine deployment due to the strong selection pressures this will place on the virus, with lessons from seasonal influenza and other viral diseases telling us that vaccine escape is something we must be ready for. Should this occur, the development of new vaccines to combat any new variants is likely to occur on a shorter timescale than the original development of COVID-19 vaccines; however there will be considerable logistical and epidemiological challenges nonetheless. Our best chance of preventing this occurring soon (which will place the greatest stress on our already stretched capacity) is with a vigorous and well-coordinated vaccine campaign now.”

 

 

https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1

 

 

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

www.sciencemediacentre.org/tag/covid-19

 

 

Declared interests

None received.

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