Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity.

TitleBroadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity.
Publication TypeJournal Article
Year of Publication2014
AuthorsBournazos S, Klein F, Pietzsch J, Seaman MS, Nussenzweig MC, Ravetch JV
JournalCell
Volume158
Issue6
Pagination1243-53
Date Published09/11/2014
ISSN1097-4172
Abstract

Broadly neutralizing antibodies (bNAbs) against HIV-1 provide both effective pre-exposure prophylaxis and treatment of HIV-1 infection in murine and nonhuman primate models, suggesting their potential use in humans. Although much is known about the role of variable domains in the neutralization breadth and potency of these bNAbs, the contribution of Fc domains to their activities is, by contrast, poorly characterized. Assessment of the in vivo activity of several bNAbs revealed that FcγR-mediated effector function contributes substantially to their capacity to block viral entry, suppress viremia, and confer therapeutic activity. Enhanced in vivo potency of anti-HIV-1 bNAbs was associated with preferential engagement of activating, but not inhibitory FcγRs, and Fc domain-engineered bNAb variants with selective binding capacity for activating FcγRs displayed augmented protective activity. These findings reveal key roles for Fc effector function in the in vivo activity of anti-HIV-1 bNAbs and provide strategies for generating bNAbs with improved efficacy.

DOI10.1016/j.cell.2014.08.023
Alternate JournalCell
PubMed ID25215485
Grant ListP01 AI081677 / AI / NIAID NIH HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
U54 AI057158 / AI / NIAID NIH HHS / United States
UL1 TR000043 / TR / NCATS NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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