Skip to Main content Skip to Navigation
Journal articles

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

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.
Document type :
Journal articles
Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03696775
Contributor : Isma Ziani Connect in order to contact the contributor
Submitted on : Thursday, June 16, 2022 - 11:09:19 AM
Last modification on : Saturday, June 25, 2022 - 3:44:16 AM

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

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, Nature Publishing Group, 2022, 13 (1), pp.662. ⟨10.1038/s41467-022-28250-7⟩. ⟨pasteur-03696775⟩

Share

Metrics

Record views

0

Files downloads

0