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© A-M. Pais-Correia, M-I. Thoulouze, A. Alcover, A. Gessain
Mise en évidence de structures de type "biofilm ", formées par le rétrovirus HTLV-1 générés par des cellules infectées (cellules du haut), qui ont été transmis à un autre lymphocyte (cellule du bas). Micrographie en microscopie électronique à balayage. Image colorisée.
Publication : Nature communications

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 03 Feb 2022

Spencer DA, Goldberg BS, Pandey S, Ordonez T, Dufloo J, Barnette P, Sutton WF, Henderson H, Agnor R, Gao L, Bruel T, Schwartz O, Haigwood NL, Ackerman ME, Hessell AJ,

Link to Pubmed [PMID] – 35115533

Link to DOI – 10.1038/s41467-022-28250-7

Nat Commun 2022 02; 13(1): 662

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 SHIVSF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy.

https://pubmed.ncbi.nlm.nih.gov/35115533