Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

James Brett Case; Samantha Mackin; John M. Errico; Zhenlu Chong; Emily A. Madden; Bradley Whitener; Barbara Guarino; Michael A. Schmid; Kim Rosenthal; Kuishu Ren; Ha V. Dang; Gyorgy Snell; Ana Jung; Lindsay Droit; Scott A. Handley; Peter J. Halfmann; Yoshihiro Kawaoka; James E. Crowe; Daved H. Fremont; Herbert W. Virgin; Yueh Ming Loo; Mark T. Esser; Lisa A. Purcell; Davide Corti; Michael S. Diamond

doi:10.1038/s41467-022-31615-7

Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

James Brett Case, Samantha Mackin, John M. Errico, Zhenlu Chong, Emily A. Madden, Bradley Whitener, Barbara Guarino, Michael A. Schmid, Kim Rosenthal, Kuishu Ren, Ha V. Dang, Gyorgy Snell, Ana Jung, Lindsay Droit, Scott A. Handley, Peter J. Halfmann, Yoshihiro Kawaoka, James E. Crowe, Daved H. Fremont, Herbert W. VirginYueh Ming Loo, Mark T. Esser, Lisa A. Purcell, Davide Corti, Michael S. Diamond

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46 Scopus citations

Abstract

Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2) in prophylactic and therapeutic settings. Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human FcγR transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.

Original language	English
Article number	3824
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-31615-7
State	Published - Dec 2022

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Case, J. B., Mackin, S., Errico, J. M., Chong, Z., Madden, E. A., Whitener, B., Guarino, B., Schmid, M. A., Rosenthal, K., Ren, K., Dang, H. V., Snell, G., Jung, A., Droit, L., Handley, S. A., Halfmann, P. J., Kawaoka, Y., Crowe, J. E., Fremont, D. H., ... Diamond, M. S. (2022). Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Nature communications, 13(1), Article 3824. https://doi.org/10.1038/s41467-022-31615-7

@article{1ec8b15cf0534ab0ae501d87b048da02,

title = "Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains",

abstract = "Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2) in prophylactic and therapeutic settings. Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human FcγR transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.",

author = "Case, {James Brett} and Samantha Mackin and Errico, {John M.} and Zhenlu Chong and Madden, {Emily A.} and Bradley Whitener and Barbara Guarino and Schmid, {Michael A.} and Kim Rosenthal and Kuishu Ren and Dang, {Ha V.} and Gyorgy Snell and Ana Jung and Lindsay Droit and Handley, {Scott A.} and Halfmann, {Peter J.} and Yoshihiro Kawaoka and Crowe, {James E.} and Fremont, {Daved H.} and Virgin, {Herbert W.} and Loo, {Yueh Ming} and Esser, {Mark T.} and Purcell, {Lisa A.} and Davide Corti and Diamond, {Michael S.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-31615-7",

language = "English",

volume = "13",

journal = "Nature communications",

issn = "2041-1723",

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Case, JB, Mackin, S, Errico, JM, Chong, Z, Madden, EA, Whitener, B, Guarino, B, Schmid, MA, Rosenthal, K, Ren, K, Dang, HV, Snell, G, Jung, A, Droit, L, Handley, SA, Halfmann, PJ, Kawaoka, Y, Crowe, JE, Fremont, DH, Virgin, HW, Loo, YM, Esser, MT, Purcell, LA, Corti, D & Diamond, MS 2022, 'Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains', Nature communications, vol. 13, no. 1, 3824. https://doi.org/10.1038/s41467-022-31615-7

TY - JOUR

T1 - Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

AU - Case, James Brett

AU - Mackin, Samantha

AU - Errico, John M.

AU - Chong, Zhenlu

AU - Madden, Emily A.

AU - Whitener, Bradley

AU - Guarino, Barbara

AU - Schmid, Michael A.

AU - Rosenthal, Kim

AU - Ren, Kuishu

AU - Dang, Ha V.

AU - Snell, Gyorgy

AU - Jung, Ana

AU - Droit, Lindsay

AU - Handley, Scott A.

AU - Halfmann, Peter J.

AU - Kawaoka, Yoshihiro

AU - Crowe, James E.

AU - Fremont, Daved H.

AU - Virgin, Herbert W.

AU - Loo, Yueh Ming

AU - Esser, Mark T.

AU - Purcell, Lisa A.

AU - Corti, Davide

AU - Diamond, Michael S.

PY - 2022/12

Y1 - 2022/12

N2 - Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2) in prophylactic and therapeutic settings. Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human FcγR transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.

AB - Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2) in prophylactic and therapeutic settings. Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human FcγR transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.

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DO - 10.1038/s41467-022-31615-7

M3 - Article

C2 - 35780162

AN - SCOPUS:85133324185

SN - 2041-1723

VL - 13

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3824

ER -

Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

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