Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency.

TitleBispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency.
Publication TypeJournal Article
Year of Publication2016
AuthorsBournazos S, Gazumyan A, Seaman MS, Nussenzweig MC, Ravetch JV
JournalCell
Volume165
Issue7
Pagination1609-20
Date Published2016 Jun 16
ISSN1097-4172
Abstract

Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) suppress viremia in animal models of HIV-1 and humans. To achieve potent activity without the emergence of viral escape mutants, co-administration of different bNAbs is necessary to target distinct epitopes essential for viral fitness. Here, we report the development of bispecific anti-Env neutralizing antibodies (biNAbs) with potent activity. Synergistic activity of biNAbs was achieved by combining an engineered hinge domain of IgG3 to increase Fab domain flexibility necessary for hetero-bivalent binding to the Env trimer while retaining the functional properties of the IgG1-Fc. Compared to unmodified biNAbs, hinge domain variants exhibited substantially improved neutralization activity, with particular combinations showing evidence of synergistic neutralization potency in vitro and enhanced in vivo therapeutic activity in HIV-1-infected humanized mice. These findings suggest innovative strategies for generating biNAbs with enhanced neutralization breadth and potency, representing ideal candidate molecules for the control of HIV-1 infection.

DOI10.1016/j.cell.2016.04.050
Alternate JournalCell
PubMed ID27315478
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