Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo

被引：209

作者：

Schafer, Alexandra ^{[1
]}

Muecksch, Frauke ^{[2
]}

Lorenzi, Julio C. C. ^{[3
]}

Leist, Sarah R. ^{[1
]}

Cipolla, Melissa ^{[3
]}

Bournazos, Stylianos ^{[4
]}

Schmidt, Fabian ^{[2
]}

Maison, Rachel M. ^{[8
]}

Gazumyan, Anna ^{[3
]}

Martinez, David R. ^{[1
]}

Baric, Ralph S. ^{[1
,5
]}

Robbiani, Davide F. ^{[3
,6
]}

Hatziioannou, Theodora ^{[2
]}

Ravetch, Jeffrey, V ^{[4
]}

Bieniasz, Paul D. ^{[2
,7
]}

Bowen, Richard A. ^{[8
]}

Nussenzweig, Michel C. ^{[3
,7
]}

Sheahan, Timothy P. ^{[1
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA

[2] Rockefeller Univ, Lab Retrovirol, 1230 York Ave, New York, NY 10021 USA

[3] Rockefeller Univ, Lab Mol Immunol, 1230 York Ave, New York, NY 10021 USA

[4] Rockefeller Univ, Lab Mol Genet & Immunol, 1230 York Ave, New York, NY 10021 USA

[5] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA

[6] Univ Svizzera Italiana, Inst Res Biomed, Bellinzona, Switzerland

[7] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

[8] Colorado State Univ, Lab Anim Reprod & Biotechnol, Ft Collins, CO 80523 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2021年 / 218卷 / 03期

关键词：

BROADLY NEUTRALIZING ANTIBODIES; FC;

D O I：

10.1084/jem.20201993

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.

引用

页数：9

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