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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2023

Complement contributes to antibody-mediated protection against repeated SHIV challenge

Benjamin Goldberg
Yun Yu

Résumé

The first clinical efficacy trials of a broadly neutralizing antibody (bNAb) resulted in less benefit than expected and suggested that improvements are needed to prevent HIV infection. While considerable effort has focused on optimizing neutralization breadth and potency, it remains unclear whether augmenting the effector functions elicited by broadly neutralizing antibodies (bNAbs) may also improve their clinical potential. Among these effector functions, complement-mediated activities, which can culminate in the lysis of virions or infected cells, have been the least well studied. Here, functionally modified variants of the second-generation bNAb 10-1074 with ablated and enhanced complement activation profiles were used to examine the role of complement-associated effector functions. When administered prophylactically against simian-HIV challenge in rhesus macaques, more bNAb was required to prevent plasma viremia when complement activity was eliminated. Conversely, less bNAb was required to protect animals from plasma viremia when complement activity was enhanced. These results suggest that complement-mediated effector functions contribute to in vivo antiviral activity, and that their engineering may contribute to the further improvements in the efficacy of antibody-mediated prevention strategies.

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Immunothérapie
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Origine : Publication financée par une institution
Licence : CC BY NC ND - Paternité - Pas d'utilisation commerciale - Pas de modification

Dates et versions

pasteur-04165265 , version 1 (18-07-2023)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Benjamin Goldberg, David Spencer, Shilpi Pandey, Tracy Ordonez, Philip Barnette, et al.. Complement contributes to antibody-mediated protection against repeated SHIV challenge. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (20), pp.e2221247120. ⟨10.1073/pnas.2221247120⟩. ⟨pasteur-04165265⟩
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