Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody

Asokan, Mangaiarkarasi; Dias, Joana; Liu, Cuiping; Maximova, Anna; Ernste, Keenan; Pegu, Amarendra; McKee, Krisha; Shi, Wei; Chen, Xuejun; Almasri, Cassandra; Promsote, Wanwisa; Ambrozak, David R.; Gama, Lucio; Hu, Jianfei; Douek, Daniel C.; Todd, John-Paul; Lifson, Jeffrey D.; Fourati, Slim; Sekaly, Rafick P.; Crowley, Andrew R.; Ackerman, Margaret E.; Ko, Sung Hee; Kilam, Divya; Boritz, Eli A.; Liao, Laura E.; Best, Katharine; Perelson, Alan S.; Mascola, John R.; Koup, Richard A.

doi:10.1073/pnas.2008236117

Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody

Journal Article · Mon Jul 20 04:00:00 EDT 2020 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2008236117· OSTI ID:1640228

^[1]; Dias, Joana ^[2]; Liu, Cuiping ^[1]; Maximova, Anna ^[1]; ^[1]; ^[1]; McKee, Krisha ^[1]; Shi, Wei ^[1]; Chen, Xuejun ^[1]; Almasri, Cassandra ^[1]; Promsote, Wanwisa ^[2]; Ambrozak, David R. ^[2]; Gama, Lucio ^[2]; Hu, Jianfei ^[3]; Douek, Daniel C. ^[3]; Todd, John-Paul ^[4]; Lifson, Jeffrey D. ^[5]; ^[6]; Sekaly, Rafick P. ^[6]; Crowley, Andrew R. ^[7] more »

Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892,
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892,
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892,
Translational Research Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892,
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701,
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106,
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755,
Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892,
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545

Significance

Neutralizing antibodies (NAbs) against HIV-1 are under clinical development. Despite demonstrated antiviral activity when used as treatment in HIV-infected people, the mechanism of action of NAbs remains controversial. Quantification of the relative contribution of Fab-mediated (neutralization of free virus) and Fc-mediated functions such as antibody-dependent cellular cytotoxicity (ADCC), phagocytosis, and complement fixation is essential to develop better therapies. Here, we treated chronically SHIV-infected rhesus macaques with a single dose of NAb VRC07-523LS with or without Fc modifications. Fc function contributes 21% to the antiviral activity of VRC07-523LS with an unmodified Fc region, when compared to NAb with Fc knockout mutations. However, NAbs with improved ADCC function in vitro did not show enhanced antiviral activity in vivo.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1640228

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 31 Vol. 117; ISSN 0027-8424

Publisher:: Proceedings of the National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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