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

David A. Spencer, Benjamin S. Goldberg, Shilpi Pandey, Tracy Ordonez, Jérémy Dufloo, Philip Barnette, William F. Sutton, Heidi Henderson, Rebecca Agnor, Lina Gao, Timothée Bruel, Olivier Schwartz, Nancy L. Haigwood, Margaret E. Ackerman and Ann J. Hessell ()
Additional contact information
David A. Spencer: Oregon National Primate Research Center, Oregon Health & Science University
Benjamin S. Goldberg: Dartmouth College
Shilpi Pandey: Oregon National Primate Research Center, Oregon Health & Science University
Tracy Ordonez: Oregon National Primate Research Center, Oregon Health & Science University
Jérémy Dufloo: Institut Pasteur
Philip Barnette: Oregon National Primate Research Center, Oregon Health & Science University
William F. Sutton: Oregon National Primate Research Center, Oregon Health & Science University
Heidi Henderson: Oregon National Primate Research Center, Oregon Health & Science University
Rebecca Agnor: Oregon Health & Science University
Lina Gao: Oregon Health & Science University
Timothée Bruel: Institut Pasteur
Olivier Schwartz: Institut Pasteur
Nancy L. Haigwood: Oregon National Primate Research Center, Oregon Health & Science University
Margaret E. Ackerman: Dartmouth College
Ann J. Hessell: Oregon National Primate Research Center, Oregon Health & Science University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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 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.

Date: 2022
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DOI: 10.1038/s41467-022-28250-7

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