Endogenous antibody responses in REGN-COV2 treated SARS-CoV-2 infected individuals

Ashwini A Kurshan; Luke Blagdon Snell; Luke Blagdon Snell; Lucie Prior; Chung Him Jerry Tam; Carl Graham; Rajeni Thangarajah; Jonathan Edgeworth; Gaia Nebbia; Katherine Doores

doi:10.1093/oxfimm/iqac012

Endogenous antibody responses in REGN-COV2 treated SARS-CoV-2 infected individuals

Ashwini A Kurshan , Luke Blagdon Snell, Luke Blagdon Snell, Lucie Prior, Chung Him Jerry Tam, Carl Graham, Rajeni Thangarajah, Jonathan Edgeworth, Gaia Nebbia, Katherine Doores

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Abstract

Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that in the majority of unvaccinated, delta-infected REGN-COV2-treated individuals, an endogenous antibody response is generated, but, like untreated, delta-infected individuals, there was a limited neutralization breadth. However, some vaccinated individuals who were seronegative at SARS-CoV-2 infection baseline and some unvaccinated individuals failed to produce an endogenous immune response following infection and REGN-COV2 treatment demonstrating the importance of mAb therapy in some patient populations.

Original language	English
Article number	iqac012
Journal	Oxford Open Immunology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1093/oxfimm/iqac012
Publication status	Published - 2023

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@article{04af19f60be24a088cf5a94b0d68bf4b,

title = "Endogenous antibody responses in REGN-COV2 treated SARS-CoV-2 infected individuals",

abstract = "Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that in the majority of unvaccinated, delta-infected REGN-COV2-treated individuals, an endogenous antibody response is generated, but, like untreated, delta-infected individuals, there was a limited neutralization breadth. However, some vaccinated individuals who were seronegative at SARS-CoV-2 infection baseline and some unvaccinated individuals failed to produce an endogenous immune response following infection and REGN-COV2 treatment demonstrating the importance of mAb therapy in some patient populations.",

author = "{A Kurshan}, Ashwini and Snell, {Luke Blagdon} and Snell, {Luke Blagdon} and Lucie Prior and Tam, {Chung Him Jerry} and Carl Graham and Rajeni Thangarajah and Jonathan Edgeworth and Gaia Nebbia and Katherine Doores",

note = "Funding Information: The authors wish to thank Leo James and Jakub Luptak for the Nucleoprotein, Wendy Barclay and Thomas Peacock (Imperial) for providing the delta, BA.1 and BA.2 Spike plasmids, and James Voss and Deli Huang (Scripps) for providing the Hela-ACE2 cells. This work was funded by Huo Family Foundation Award to K.J.D. and Medical Research Council (MRC) Genotype-to-Phenotype UK National Virology Consortium (MR/W005611/1 to K.J.D.). 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 programme supported by the European Union (grant number RIA2020EF-3008 COVAB). The views and opinions of the authors expressed herein 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 (K.J.D.). Publisher Copyright: {\textcopyright} The Author(s) 2023. Published by Oxford University Press.",

year = "2023",

doi = "10.1093/oxfimm/iqac012",

language = "English",

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journal = "Oxford Open Immunology",

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AU - A Kurshan , Ashwini

AU - Snell, Luke Blagdon

AU - Prior, Lucie

AU - Tam, Chung Him Jerry

AU - Graham, Carl

AU - Thangarajah, Rajeni

AU - Edgeworth, Jonathan

AU - Nebbia, Gaia

AU - Doores, Katherine

N1 - Funding Information: The authors wish to thank Leo James and Jakub Luptak for the Nucleoprotein, Wendy Barclay and Thomas Peacock (Imperial) for providing the delta, BA.1 and BA.2 Spike plasmids, and James Voss and Deli Huang (Scripps) for providing the Hela-ACE2 cells. This work was funded by Huo Family Foundation Award to K.J.D. and Medical Research Council (MRC) Genotype-to-Phenotype UK National Virology Consortium (MR/W005611/1 to K.J.D.). 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 programme supported by the European Union (grant number RIA2020EF-3008 COVAB). The views and opinions of the authors expressed herein 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 (K.J.D.). Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press.

PY - 2023

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N2 - Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that in the majority of unvaccinated, delta-infected REGN-COV2-treated individuals, an endogenous antibody response is generated, but, like untreated, delta-infected individuals, there was a limited neutralization breadth. However, some vaccinated individuals who were seronegative at SARS-CoV-2 infection baseline and some unvaccinated individuals failed to produce an endogenous immune response following infection and REGN-COV2 treatment demonstrating the importance of mAb therapy in some patient populations.

AB - Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that in the majority of unvaccinated, delta-infected REGN-COV2-treated individuals, an endogenous antibody response is generated, but, like untreated, delta-infected individuals, there was a limited neutralization breadth. However, some vaccinated individuals who were seronegative at SARS-CoV-2 infection baseline and some unvaccinated individuals failed to produce an endogenous immune response following infection and REGN-COV2 treatment demonstrating the importance of mAb therapy in some patient populations.

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DO - 10.1093/oxfimm/iqac012

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JF - Oxford Open Immunology

IS - 1

M1 - iqac012

ER -

Endogenous antibody responses in REGN-COV2 treated SARS-CoV-2 infected individuals

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