Revisiting an IgG Fc Loss-of-Function Experiment: the Role of Complement in HIV Broadly Neutralizing Antibody b12 Activity

Author:

Goldberg Benjamin S.1,Kaku Chengzi I.1,Dufloo Jérémy2,Bruel Timothée2,Schwartz Olivier2,Spencer David A.3,Hessell Ann J.3,Ackerman Margaret E.14ORCID

Affiliation:

1. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA

2. Virus and Immunity Unit, Department of Virology, Institut Pasteur, Paris, France

3. Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA

4. Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA

Abstract

Given the suboptimal outcome of VRC01 antibody-mediated prevention of HIV-1 infection in its first field trial, means to improve diverse antiviral activities in vivo have renewed importance. This work revisits a loss-of-function experiment that investigated the mechanism of action of b12, a similar antibody, and finds that the reason why complement-mediated antiviral activities were not observed to contribute to protection may be the inherent lack of activity of wild-type b12, raising the prospect that this mechanism may contribute in the context of other HIV-specific antibodies.

Funder

HHS | National Institutes of Health

Fondation pour la Recherche Médicale

Agence Nationale de Recherches sur le Sida et les Hépatites Virales

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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