Pfizer-BioNTech COVID Vaccine Recipients Have Lower Antibody Levels Targeting the India (Delta / B.1.617.2) Variant

Levels of antibodies in the blood of vaccinated people who can recognize and fight the new SARS-CoV-2 Delta variant first discovered in India (B.1.617.2) are on average lower than those against previously circulating variants in the UK, according to new lab data from the Francis Crick Institute and the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre, published June 3, 2021 as a research letter in The Lancet.

The results also show that levels of these antibodies decrease with age and levels decline over time, providing additional evidence to support plans to boost vaccinations for vulnerable people in the fall.

And the researchers support current plans to narrow the dose gap between vaccines, as they found that after just one dose of the Pfizer-BioNTech vaccine, people are less likely to develop antibody levels against the B.1.617.2 (Delta) variant if high. as that seen against the previously dominant B.1.1.7 (Alpha) variant, first found in Kent.

While lab results like these are needed to provide guidance on how the virus might evolve to escape first-generation vaccines, antibody levels alone do not predict vaccine effectiveness and prospective population studies are also needed. Lower neutralizing antibody levels may still be associated with protection against COVID-19.

This is the largest study published to date on the neutralizing potential of vaccines against the latest variants of concern in healthy adults. Researchers have submitted their findings to the Genotype-to-Phenotype National Virology Consortium (G2P-UK), the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG), and the Joint Committee on Vaccination and Immunization (JCVI), as evidence of the level protection that people can receive against the new variants after one dose and both doses of the Pfizer COVID-19 vaccine.

As part of the SARS-CoV-2 Legacy study, led by the Crick and partners from UCL and University College London Hospitals NHS Foundation Trust (UCLH), health professionals and staff at the institutions regularly donate blood and swabs so that researchers can monitor the changing infection risk and response to vaccination.

Samples of the latest variants of concern provided by NHS labs to the G2P-UK consortium have allowed researchers to quickly assess the potential risks they may pose.

Within just a few days of having enough of each variant to study, they were able to analyze antibodies in the blood of 250 healthy people who received one or two doses of the Pfizer-BioNTech Covid-19 vaccine, up to three. months after their first dose. Using a new, highly accurate, high-throughput viral neutralization assay developed at the Crick, they tested the ability of antibodies to block the virus’s entry into cells, called “neutralizing antibodies,” against five different variants of SARS-CoV. -2:

The original species first discovered in Wuhan, China The dominant species in Europe during the first wave in April 2020 (D614G) B.1.1.7, the variant first discovered in Kent, UK (Alpha) B.1.351 , the variant first discovered in South Africa (beta) B.1.617.2, the newest variant of concern, first discovered in India (Delta)

They then compared the concentrations of these neutralizing antibodies between all variants. Data from previous clinical studies suggest that higher antibody titers (the highest level of dilution that still blocks 50% of virus infection in the lab) is a good predictor of vaccine efficacy and better protection against COVID-19.

They found that in people who had been fully vaccinated with two doses of the Pfizer-BioNTech vaccine, the levels of neutralizing antibodies were more than five times lower against the B.1,617.2 variant compared to the parent strain, on which the current strains are present. vaccines are based.

Importantly, this antibody response was even lower in people who had received only one dose. After a single dose of Pfizer-BioNTech, 79% of people had a quantifiable neutralizing antibody response to the parent strain, but this decreased to 50% for B.1.1.7, 32% for B.1.617.2 and 25% for B.1.351 .

Although antibody levels decreased with age in all variants, no correlation was observed for gender or BMI.

The study participants analyzed here were all vaccinated with the Pfizer-BioNTech vaccine. More work is underway to test neutralizing antibodies against the same variants in people vaccinated with the Oxford/AstraZeneca vaccine.

Emma Wall, UCLH Infectious Diseases consultant and Senior Clinical Research Fellow for the Legacy study, said: “This virus is likely to be around for a while, so we need to remain agile and vigilant. Our research is designed to respond to shifts in the pandemic so we can quickly provide evidence about evolving risks and protections.

“The most important thing is to ensure that vaccine protection remains high enough to keep as many people out of the hospital as possible. And our results suggest that the best way to do this is to quickly administer second doses and boosters to those whose immunity may not be high enough against these new variants.

David LV Bauer, group leader of Crick’s RNA Virus Replication Laboratory and member of the G2P-UK National Virology Consortium, said: “New variants occur naturally and those that have an advantage will spread. We now have the opportunity to quickly adapt vaccination strategies to maximize protection where we know people are most vulnerable.

“Keeping up with these evolutionary changes is essential for us to maintain control of the pandemic and return to normalcy. This work is a powerful example of effective collaborations between NHS and academic colleagues, which can help us navigate changes in this new phase of the pandemic.”

Reference: “Neutralizing antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination” by Emma C Wall, Mary Wu, Ruth Harvey, Gavin Kelly, Scott Warchal, Chelsea Sawyer, Rodney Daniels, Philip Hobson, Emine Hatipoglu, Yenting Ngai, Saira Hussain, Jerome Nicod, Robert Goldstone, Karen Ambrose, Steve Hindmarsh, Rupert Beale, Andrew Riddell, Steve Gamblin, Michael Howell, George Kassiotis, Vincenzo Libri, Bryan Williams, Charles Swanton, Sonia Gandhi and David L.V. Bauer, June 3, 2021, The Lancet.
DOI: 10.1016/S0140-6736(21) 01290-3