Broad Neutralization of SARS-CoV-2 Variants, Including Omicron, following Breakthrough Infection with Delta in COVID-19-Vaccinated Individuals

Thomas Lechmere; Luke Blagdon Snell; Carl Graham; Jeffrey Seow; Zayed Shalim; Themoula Charalampous; Adela Alcolea-Medina; Rahul Batra; Gaia Nebbia; Jonathan Edgeworth; Michael Malim; Katherine Doores

doi:10.1128/mbio.03798-21

Broad Neutralization of SARS-CoV-2 Variants, Including Omicron, following Breakthrough Infection with Delta in COVID-19-Vaccinated Individuals

Thomas Lechmere, Luke Blagdon Snell, Carl Graham, Jeffrey Seow, Zayed Shalim, Themoula Charalampous, Adela Alcolea-Medina, Rahul Batra, Gaia Nebbia, Jonathan Edgeworth, Michael Malim, Katherine Doores

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Abstract

Numerous studies have shown that a prior SARS-CoV-2 infection can greatly enhance the antibody response to COVID-19 vaccination, with this so called "hybrid immunity" leading to greater neutralization breadth against SARS-CoV-2 variants of concern. However, little is known about how breakthrough infection (BTI) in COVID-19-vaccinated individuals will impact the magnitude and breadth of the neutralizing antibody response. Here, we compared neutralizing antibody responses between unvaccinated and COVID-19-double-vaccinated individuals (including both AZD1222 and BNT162b2 vaccinees) who have been infected with the Delta (B.1.617.2) variant. Rapid production of spike-reactive IgG was observed in the vaccinated group, providing evidence of effective vaccine priming. Overall, potent cross-neutralizing activity against current SARS-CoV-2 variants of concern was observed in the BTI group compared to the infection group, including neutralization of the Omicron (B.1.1.529) variant. This study provides important insights into population immunity where transmission levels remain high and in the context of new or emerging variants of concern.

Original language	English
Journal	Mbio
Volume	13
Issue number	2
Early online date	17 Mar 2022
DOIs	https://doi.org/10.1128/mbio.03798-21
Publication status	Published - 17 Mar 2022

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10.1128/mbio.03798-21

Broad Neutralization of_LECHMERE_Publishedonline17March2022_GOLD VoRFinal published version, 1.4 MBLicence: CC BY

Cite this

@article{6241b65e3b1a4bc1ac074877a27b2060,

title = "Broad Neutralization of SARS-CoV-2 Variants, Including Omicron, following Breakthrough Infection with Delta in COVID-19-Vaccinated Individuals",

abstract = "Numerous studies have shown that a prior SARS-CoV-2 infection can greatly enhance the antibody response to COVID-19 vaccination, with this so called {"}hybrid immunity{"} leading to greater neutralization breadth against SARS-CoV-2 variants of concern. However, little is known about how breakthrough infection (BTI) in COVID-19-vaccinated individuals will impact the magnitude and breadth of the neutralizing antibody response. Here, we compared neutralizing antibody responses between unvaccinated and COVID-19-double-vaccinated individuals (including both AZD1222 and BNT162b2 vaccinees) who have been infected with the Delta (B.1.617.2) variant. Rapid production of spike-reactive IgG was observed in the vaccinated group, providing evidence of effective vaccine priming. Overall, potent cross-neutralizing activity against current SARS-CoV-2 variants of concern was observed in the BTI group compared to the infection group, including neutralization of the Omicron (B.1.1.529) variant. This study provides important insights into population immunity where transmission levels remain high and in the context of new or emerging variants of concern.",

author = "Thomas Lechmere and Snell, {Luke Blagdon} and Carl Graham and Jeffrey Seow and Zayed Shalim and Themoula Charalampous and Adela Alcolea-Medina and Rahul Batra and Gaia Nebbia and Jonathan Edgeworth and Michael Malim and Katherine Doores",

note = "Funding Information: This work was funded by Fondation Dormeur, Vaduz for funding equipment to K.J.D., a Huo Family Foundation Award to M.H.M. and K.J.D., the MRC Genotype-to-Phenotype UK National Virology Consortium ([MR/W005611/1] to M.H.M. and K.J.D.). This research was funded in part by the Wellcome Trust [106223/Z/14/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. C.G. is supported by the MRC-KCL Doctoral Training Partnership in Biomedical Sciences [MR/N013700/1]. This work was supported by the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London and King{\textquoteright}s College Hospital NHS Foundation Trust. This study is part of the EDCTP2 program supported by the European Union (grant number RIA2020EF-3008 COVAB). The views and opinions of authors expressed here do not necessarily state or reflect those of EDCTP. 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). Publisher Copyright: {\textcopyright} 2022 Lechmere et al.",

year = "2022",

month = mar,

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doi = "10.1128/mbio.03798-21",

language = "English",

volume = "13",

journal = "Mbio",

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T1 - Broad Neutralization of SARS-CoV-2 Variants, Including Omicron, following Breakthrough Infection with Delta in COVID-19-Vaccinated Individuals

AU - Lechmere, Thomas

AU - Snell, Luke Blagdon

AU - Graham, Carl

AU - Seow, Jeffrey

AU - Shalim, Zayed

AU - Charalampous, Themoula

AU - Alcolea-Medina, Adela

AU - Batra, Rahul

AU - Nebbia, Gaia

AU - Edgeworth, Jonathan

AU - Malim, Michael

AU - Doores, Katherine

N1 - Funding Information: This work was funded by Fondation Dormeur, Vaduz for funding equipment to K.J.D., a Huo Family Foundation Award to M.H.M. and K.J.D., the MRC Genotype-to-Phenotype UK National Virology Consortium ([MR/W005611/1] to M.H.M. and K.J.D.). This research was funded in part by the Wellcome Trust [106223/Z/14/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. C.G. is supported by the MRC-KCL Doctoral Training Partnership in Biomedical Sciences [MR/N013700/1]. This work was 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 program supported by the European Union (grant number RIA2020EF-3008 COVAB). The views and opinions of authors expressed here do not necessarily state or reflect those of EDCTP. 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). Publisher Copyright: © 2022 Lechmere et al.

PY - 2022/3/17

Y1 - 2022/3/17

N2 - Numerous studies have shown that a prior SARS-CoV-2 infection can greatly enhance the antibody response to COVID-19 vaccination, with this so called "hybrid immunity" leading to greater neutralization breadth against SARS-CoV-2 variants of concern. However, little is known about how breakthrough infection (BTI) in COVID-19-vaccinated individuals will impact the magnitude and breadth of the neutralizing antibody response. Here, we compared neutralizing antibody responses between unvaccinated and COVID-19-double-vaccinated individuals (including both AZD1222 and BNT162b2 vaccinees) who have been infected with the Delta (B.1.617.2) variant. Rapid production of spike-reactive IgG was observed in the vaccinated group, providing evidence of effective vaccine priming. Overall, potent cross-neutralizing activity against current SARS-CoV-2 variants of concern was observed in the BTI group compared to the infection group, including neutralization of the Omicron (B.1.1.529) variant. This study provides important insights into population immunity where transmission levels remain high and in the context of new or emerging variants of concern.

AB - Numerous studies have shown that a prior SARS-CoV-2 infection can greatly enhance the antibody response to COVID-19 vaccination, with this so called "hybrid immunity" leading to greater neutralization breadth against SARS-CoV-2 variants of concern. However, little is known about how breakthrough infection (BTI) in COVID-19-vaccinated individuals will impact the magnitude and breadth of the neutralizing antibody response. Here, we compared neutralizing antibody responses between unvaccinated and COVID-19-double-vaccinated individuals (including both AZD1222 and BNT162b2 vaccinees) who have been infected with the Delta (B.1.617.2) variant. Rapid production of spike-reactive IgG was observed in the vaccinated group, providing evidence of effective vaccine priming. Overall, potent cross-neutralizing activity against current SARS-CoV-2 variants of concern was observed in the BTI group compared to the infection group, including neutralization of the Omicron (B.1.1.529) variant. This study provides important insights into population immunity where transmission levels remain high and in the context of new or emerging variants of concern.

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U2 - 10.1128/mbio.03798-21

DO - 10.1128/mbio.03798-21

M3 - Article

SN - 2150-7511

VL - 13

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JF - Mbio

IS - 2

ER -

Broad Neutralization of SARS-CoV-2 Variants, Including Omicron, following Breakthrough Infection with Delta in COVID-19-Vaccinated Individuals

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