Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

Lee, Benhur, Davis, Chris, Logan, Nicola, Tyson, Grace, Orton, Richard, Harvey, William T., Perkins, Jonathan S., Mollett, Guy, Blacow, Rachel M., Peacock, Thomas P., Barclay, Wendy S., Cherepanov, Peter, Palmarini, Massimo, Murcia, Pablo R., Patel, Arvind H., Robertson, David L., Haughney, John, Thomson, Emma C., Willett, Brian J., Bashton, Matthew, Smith, Darren, Nelson, Andrew, Young, Greg, McCann, Clare, Yew, Wen Chyin and The COVID-19 Genomics UK (COG-UK) Consortium, on behalf of the COVID-19 DeplOyed VaccinE (DOVE) Cohort Study (2021) Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination. PLOS Pathogens, 17 (12). e1010022. ISSN 1553-7374

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Official URL: https://doi.org/10.1371/journal.ppat.1010022

Abstract

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Item Type: Article
Additional Information: Matthew Bashton, Darren L. Smith, Gregory R. Young, Clare McCann, Andrew Nelson and Wen Chyin Yew are members of the COVID-19 Genomics UK (COG-UK) Consortium. Funding information: The COVID-19 DeplOyed VaccinE (DOVE) study is funded by the Medical Research Council core award (MC UU 1201412; M.P) We acknowledge the support of the G2P-UK National Virology Consortium (MR/W005611/1) funded by the UKRI (M.P.,E.C.T.). COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute (G.M., R.M.B., D.L.R., E.C.T.). W.T.H. is funded by the MRC (MR/R024758/1). N.L. and B.J.W. were funded by the Biotechnology and Biological Sciences Research Council (BBSRC, BB/R004250/1), G.T. was funded by the Department of Health and Social Care (DHSC, BB/R019843/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are indebted to Therese McSorley for recruiting participants to the DOVE study. We thank all the researchers who have shared genome data openly via the GISAID Initiative.
Subjects: B100 Anatomy, Physiology and Pathology
B200 Pharmacology, Toxicology and Pharmacy
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 25 Jan 2022 09:35
Last Modified: 25 Jan 2022 09:45
URI: http://nrl.northumbria.ac.uk/id/eprint/48239

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