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Complement contributes to antibody-mediated protection against repeated SHIV challenge.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 5/16/2023, Vol. 120 Issue 20, p1-11, 14p
- Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- IMMUNE response
HIV infections
RHESUS monkeys
COMPLEMENT activation
IMMUNOTECHNOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 120
- Issue :
- 20
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 163732140
- Full Text :
- https://doi.org/10.1073/pnas.2221247120