The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS-CoV-2 variants of concern

TY - JOUR

T1 - The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS-CoV-2 variants of concern

AU - Graham, Carl

AU - Lechmere, Thomas

AU - Rehman, Aisha

AU - Seow, Jeffrey

AU - Kurshan, Ashwini

AU - Huettner, Isabella

AU - Maguire, Thomas J.A.

AU - Tam, Jerry

AU - Cox, Daniel

AU - Ward, Christopher

AU - Racz, Mariusz

AU - Waters, Anele

AU - Mant, Christine

AU - Malim, Michael H.

AU - Fox, Julie

AU - Doores, Katie J.

N1 - Funding Information: This work was funded by Huo Family Foundation Award to MHM and KJD, MRC Genotype-to-Phenotype UK National Virology Consortium ([MR/W005611/1] to MHM and KJD), Fondation Dormeur, Vaduz for funding equipment to KJD, Wellcome Trust Investigator Award [222433/Z/21/Z] to MHM, and Wellcome Trust Multi-User Equipment Grant [208354/Z/17/Z] to MHM and KJD. CG was supported by the MRC-KCL Doctoral Training Partnership in Biomedical Sciences [MR/N013700/1]. DC was supported by a BBSRC CASE in partnership with GlaxoSmithKline [BB/V509632/1]. This work and the Infectious Diseases Biobank (CM) were supported by the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. This study is part of the EDCTP2 programme supported by the European Union (grant number RIA2020EF-3008 COVAB) (KJD, JF, MHM). This project is supported by a joint initiative between the Botnar Research Centre for Child Health and the European & Developing Countries Clinical Trials Partnership (KJD and JF). This research was funded in whole, or in part, by the Wellcome Trust [ [222433/Z/21/Z] and [208354/Z/ 17/Z]. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Philip Brouwer, Marit van Gils and Rogier Sanders for the Spike protein construct, Leo James and Jakub Luptak for the N protein, Wendy Barclay for providing the B.1.617.2, BA.1, BA.2 and BA.4/BA.5 Spike plasmids and James Voss and Deli Huang for providing the Hela-ACE2 cells. The views and opinions of authors expressed herein do not necessarily state or reflect those of EDCTP. Publisher Copyright: © 2022 Graham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/10

Y1 - 2022/10

N2 - COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3–4 week) or extended interval (8–12 weeks) and following a third vaccination approximately 6–8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low.

AB - COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3–4 week) or extended interval (8–12 weeks) and following a third vaccination approximately 6–8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low.

UR - http://www.scopus.com/inward/record.url?scp=85139907597&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1010882

DO - 10.1371/journal.ppat.1010882

M3 - Article

C2 - 36191037

AN - SCOPUS:85139907597

SN - 1553-7366

VL - 18

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 10

M1 - e1010882

ER -