Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
Name
nihms824957.pdf
Description
Accepted version
Size
1.41 MB
Format
Adobe PDF
Checksum (MD5)
a69f4f3a9b18e896d119172f05757530
Author(s)
Huang, Yunda
Ferrari, Guido
Alter, Galit
Forthal, Donald N
Kappes, John C
Lewis, George K
Love, J Christopher
Borate, Bhavesh
Harris, Linda
Greene, Kelli
Date Issued
2016
Journal
Journal of immunology
Publisher
The American Association of Immunologists
Citation
Huang, Y., et al. "Diversity of Antiviral Igg Effector Activities Observed in Hiv-Infected and Vaccinated Subjects." J Immunol 197 12 (2016): 4603-12.
Version
Author's final manuscript
Abstract
Copyright ©2016 by The American Association of Immunologists, Inc. Diverse Ab effector functions mediated by the Fc domain have been commonly associated with reduced risk of infection in a growing number of nonhuman primate and human clinical studies. This study evaluated the anti-HIVAb effector activities in polyclonal serum samples from HIV-infected donors, VAX004 vaccine recipients, and healthy HIV-negative subjects using a variety of primary and cell line-based assays, including Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cell-mediated viral inhibition, and Abdependent cellular phagocytosis. Additional assay characterization was performed with a panel of Fc-engineered variants of mAb b12. The goal of this study was to characterize different effector functions in the study samples and identify assays that might most comprehensively and dependably capture Fc-mediated Ab functions mediated by different effector cell types and against different viral targets. Deployment of such assays may facilitate assessment of functionally unique humoral responses and contribute to identification of correlates of protection with potential mechanistic significance in future HIV vaccine studies. Multivariate and correlative comparisons identified a set of Ab-dependent cell-mediated viral inhibition and phagocytosis assays that captured different Ab activities and were distinct from a group of ADCC assays that showed a more similar response profile across polyclonal serum samples. The activities of a panel of b12 monoclonal Fc variants further identified distinctions among the ADCC assays. These results reveal the natural diversity of Fc-mediated Ab effector responses among vaccine recipients in the VAX004 trial and in HIV-infected subjects, and they point to the potential importance of polyfunctional Ab responses.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.4049/JIMMUNOL.1601197
