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

Alexandra Schäfer; Frauke Muecksch; Julio C.C. Lorenzi; Sarah R. Leist; Melissa Cipolla; Stylianos Bournazos; Fabian Schmidt; Rachel M. Maison; Anna Gazumyan; David R. Martinez; Ralph S. Baric; Davide F. Robbiani; Theodora Hatziioannou; Jeffrey V. Ravetch; Paul D. Bieniasz; Richard A. Bowen; Michel C. Nussenzweig; Timothy P. Sheahan

doi:10.1084/JEM.20201993

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

Alexandra Schäfer, Frauke Muecksch, Julio C.C. Lorenzi, Sarah R. Leist, Melissa Cipolla, Stylianos Bournazos, Fabian Schmidt, Rachel M. Maison, Anna Gazumyan, David R. Martinez, Ralph S. Baric, Davide F. Robbiani, Theodora Hatziioannou, Jeffrey V. Ravetch, Paul D. Bieniasz, Richard A. Bowen, Michel C. Nussenzweig, Timothy P. Sheahan

Research output: Contribution to journal › Article › peer-review

202 Scopus citations

Abstract

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.

Original language	English (US)
Journal	Journal of Experimental Medicine
Volume	218
Issue number	3
DOIs	https://doi.org/10.1084/JEM.20201993
State	Published - Jan 1 2020
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1084/JEM.20201993

Cite this

Schäfer, A., Muecksch, F., Lorenzi, J. C. C., Leist, S. R., Cipolla, M., Bournazos, S., Schmidt, F., Maison, R. M., Gazumyan, A., Martinez, D. R., Baric, R. S., Robbiani, D. F., Hatziioannou, T., Ravetch, J. V., Bieniasz, P. D., Bowen, R. A., Nussenzweig, M. C., & Sheahan, T. P. (2020). Antibody potency, effector function, and combinations in protection and therapy for SARS-cov-2 infection in vivo. Journal of Experimental Medicine, 218(3). https://doi.org/10.1084/JEM.20201993

@article{c42cb0d5432943ac9b444c6b939ae332,

title = "Antibody potency, effector function, and combinations in protection and therapy for SARS-cov-2 infection in vivo",

abstract = "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.",

author = "Alexandra Sch{\"a}fer and Frauke Muecksch and Lorenzi, {Julio C.C.} and Leist, {Sarah R.} and Melissa Cipolla and Stylianos Bournazos and Fabian Schmidt and Maison, {Rachel M.} and Anna Gazumyan and Martinez, {David R.} and Baric, {Ralph S.} and Robbiani, {Davide F.} and Theodora Hatziioannou and Ravetch, {Jeffrey V.} and Bieniasz, {Paul D.} and Bowen, {Richard A.} and Nussenzweig, {Michel C.} and Sheahan, {Timothy P.}",

note = "Generated from Scopus record by KAUST IRTS on 2023-02-15",

year = "2020",

month = jan,

day = "1",

doi = "10.1084/JEM.20201993",

language = "English (US)",

volume = "218",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "3",

}

Schäfer, A, Muecksch, F, Lorenzi, JCC, Leist, SR, Cipolla, M, Bournazos, S, Schmidt, F, Maison, RM, Gazumyan, A, Martinez, DR, Baric, RS, Robbiani, DF, Hatziioannou, T, Ravetch, JV, Bieniasz, PD, Bowen, RA, Nussenzweig, MC & Sheahan, TP 2020, 'Antibody potency, effector function, and combinations in protection and therapy for SARS-cov-2 infection in vivo', Journal of Experimental Medicine, vol. 218, no. 3. https://doi.org/10.1084/JEM.20201993

TY - JOUR

T1 - Antibody potency, effector function, and combinations in protection and therapy for SARS-cov-2 infection in vivo

AU - Schäfer, Alexandra

AU - Muecksch, Frauke

AU - Lorenzi, Julio C.C.

AU - Leist, Sarah R.

AU - Cipolla, Melissa

AU - Bournazos, Stylianos

AU - Schmidt, Fabian

AU - Maison, Rachel M.

AU - Gazumyan, Anna

AU - Martinez, David R.

AU - Baric, Ralph S.

AU - Robbiani, Davide F.

AU - Hatziioannou, Theodora

AU - Ravetch, Jeffrey V.

AU - Bieniasz, Paul D.

AU - Bowen, Richard A.

AU - Nussenzweig, Michel C.

AU - Sheahan, Timothy P.

N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

UR - https://rupress.org/jem/article/218/3/e20201993/211549/Antibody-potency-effector-function-and

UR - http://www.scopus.com/inward/record.url?scp=85096509078&partnerID=8YFLogxK

U2 - 10.1084/JEM.20201993

DO - 10.1084/JEM.20201993

M3 - Article

SN - 0022-1007

VL - 218

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 3

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this