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Pfizer/BioNTech vaccine and Covid-19 variants: What University of Cambridge study tells us





University of Cambridge research suggests Pfizer/BioNTech’s Covid-19 vaccine should still provide protection against the Kent variant of the virus - but the mutation seen in the South African variant is a cause of greater concern.

The early findings, which have yet to be peer-reviewed, underscore the importance of the second dose. The study suggests that people aged over-80 may not be able to produce sufficient antibodies to counteract the E484K mutation – first seen in the South African variant, but now appearing in other strains - until they have had their follow-up jab.

Prof Ravi Gupta. Picture: Homerton College
Prof Ravi Gupta. Picture: Homerton College

The researchers, from the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), stress that their study was carried out in only a small number of patients.

Exploring the B1.1.7 variant - the so-called Kent variant discovered before Christmas by the Cambridge-led Covid-19 Genomics UK (COG-UK) Consortium - they found it required about a two-fold increase in antibodies to counteract.

But the E484K mutation needed an almost tenfold increase in antibodies to neutralise it.

Professor Ravi Gupta from CITIID, who led the study, said: “Our findings suggest that the Pfizer / BioNTech vaccine is likely to offer similar protection against B1.1.7 as it does against the previous strain of SARS-CoV-2.

“Although we found a reduction in the ability of antibodies to neutralise the virus, given the number of antibodies produced following vaccination, this should still only have a relatively modest effect and people should still be protected.

“Of particular concern, though, is the emergence of the E484K mutation, which so far has only been seen in a relatively small number of individuals. Our work suggests the vaccine is likely to be less effective when dealing with this mutation.

“B1.1.7 will continue to acquire mutations seen in the other variants of concern, so we need to plan for the next generation of vaccines to have modifications to account for new variants. We also need to scale up vaccines as fast and as broadly as possible to get transmission down globally.”

Professor Ravi Gupta, of the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) in the Department of Medicine at the University of Cambridge
Professor Ravi Gupta, of the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) in the Department of Medicine at the University of Cambridge

The researchers released the data ahead of peer review because of the urgent need to share information on the pandemic, particularly amid the rapid spread of the Kent variant, which has been shown to be more easily transmissible.

Researchers in Cambridge and at COG-UK now report seeing a number of virus sequences that also include the E484K mutation, first seen in the South African variant.

The research was supported by Wellcome, the Medical Research Council, the Bill and Melinda Gates Foundation and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

How the research was conducted

Blood samples from 26 individuals who had received their first dose of the Pfizer vaccine three weeks earlier were used to extract serum by researchers at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) at the University of Cambridge.

They obtained the samples by working with the NIHR Covid-19 BioResource, through which volunteers are able to offer to take part in research.

The serum from the volunteers, who ranged in age from 29 to 89, contained antibodies raised in response to the vaccine.

A vaccine, with an image of the Covid-19 virus behind
A vaccine, with an image of the Covid-19 virus behind

Working in secure conditions, the team created a synthetic version of the SARS-CoV-2 virus, which is known as a pseudovirus, against which they tested the individuals’ sera.

They found that all but seven of the individuals had levels of antibodies sufficiently high to neutralise this version of the virus, indicating that the vaccine offered protection against infection.

They then added all eight mutations to the spike protein that are found in B1.1.7 - the Kent variant - to the pseudovirus.

This demonstrated that the efficacy of the vaccine was affected by these mutations and higher concentrations of antibody in the sera were needed to neutralise the virus.

They report wide variation between individuals, but on average B1.1.7 required around a two-fold increase in the concentration of serum antibody.

When the E484K mutation first seen in the South African variant, and now elsewhere, was added, they found substantially higher levels of antibody were required.

How the Pfizer/BioNTech vaccine works. Graphic: PA
How the Pfizer/BioNTech vaccine works. Graphic: PA

On average, this mutation required an almost ten-fold increase in the concentration of serum antibody for neutralisation compared to the strain circulating prior to the emergence of B.1.1.7.

Seven involved in the study were unable to neutralise the virus after the first dose - all aged over 80 years old. These represented almost half of the 15 individuals aged over 80.

But the more encouraging news was that at a follow-up visit, after these individuals had received their second dose of the vaccine three weeks later, they were all able to neutralise the virus.

Dr Dami Collier, the main co-investigator on the studies, added: “Our data suggest that a significant proportion of people aged over 80 may not have developed protective neutralising antibodies against infection three weeks after their first dose of the vaccine.

“But it’s reassuring to see that after two doses, serum from every individual was able to neutralise the virus.”

What about the Oxford University / AstraZeneca vaccine?

The Cambridge study focused on the Pfizer/BioNTech vaccine.

But Oxford University and AstraZeneca are expected to publish data in the coming days about the efficacy of their vaccine against the new variants.

Two Covid-19 vaccines are being rolled out
Two Covid-19 vaccines are being rolled out

Oxford has said it expects “the findings to be broadly similar to those already reported by fellow vaccine developers”.

In the meantime, they have published encouraging data from a new study that showed their jab offers 76 per cent protection up to three months after the first dose and could reduce transmission by 67 per cent.

The data suggests that it is the dosing interval and not the dosing level, which has a great impact on the efficacy of their vaccine.

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