Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates

Lars Hangartner, David Beauparlant, Eva Rakasz, Rebecca Nedellec, Nathanaël Hozé, Katherine McKenney, Mauricio A. Martins, Gemma E. Seabright, Joel D. Allen, Andrea M. Weiler, Thomas C. Friedrich, Roland R. Regoes, Max Crispin, Dennis R. Burton

Research output: Contribution to journalArticlepeer-review

Abstract

Protection from immunodeficiency virus challenge in nonhuman primates (NHPs) by a first-generation HIV broadly neutralizing antibody (bnAb) b12 has previously been shown to benefit from interaction between the bnAb and Fcγ receptors (FcγRs) on immune cells. To investigate the mechanism of protection for a more potent second-generation bnAb currently in clinical trials, PGT121, we carried out a series of NHP studies. These studies included treating with PGT121 at a concentration at which only half of the animals were protected to avoid potential masking of FcγR effector function benefits by dominant neutralization and using a new variant that more completely eliminated all rhesus FcγR binding than earlier variants. In contrast to b12, which required FcγR binding for optimal protection, we concluded that PGT121-mediated protection is not augmented by FcγR interaction. Thus, for HIV-passive antibody prophylaxis, these results, together with existing literature, emphasize the importance of neutralization potency for clinical antibodies, with effector function requiring evaluation for individual antibodies.

Original languageEnglish (US)
Article numbereabe3349
JournalScience Translational Medicine
Volume13
Issue number585
DOIs
StatePublished - Mar 17 2021
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates'. Together they form a unique fingerprint.

Cite this