Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis - Institut Pasteur Access content directly
Journal Articles Nature Communications Year : 2022

Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

David Spencer

Abstract

Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C’) activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78–88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C’ functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIV SF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy.

Domains

Virology
Fichier principal
Vignette du fichier
s41467-022-28250-7.pdf (1.25 Mo) Télécharger le fichier

Dates and versions

pasteur-03696775 , version 1 (16-06-2022)

Licence

Attribution

Identifiers

Cite

David Spencer, Benjamin Goldberg, Shilpi Pandey, Tracy Ordonez, Jérémy Dufloo, et al.. Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis. Nature Communications, 2022, 13 (1), pp.662. ⟨10.1038/s41467-022-28250-7⟩. ⟨pasteur-03696775⟩
56 View
60 Download

Altmetric

Share

Gmail Facebook X LinkedIn More