Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects

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 act...

Full description

Bibliographic Details
Main Authors: Huang, Yunda, Ferrari, Guido, Alter, Galit, Forthal, Donald N, Kappes, John C, Lewis, George K, Love, J Christopher, Borate, Bhavesh, Harris, Linda, Greene, Kelli, Gao, Hongmei, Phan, Tran B, Landucci, Gary, Goods, Brittany A, Dowell, Karen G, Cheng, Hao D, Bailey-Kellogg, Chris, Montefiori, David C, Ackerman, Margaret E
Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering
Format: Article
Language:English
Published: The American Association of Immunologists 2021
Online Access:https://hdl.handle.net/1721.1/133926
_version_ 1826201098201858048
author Huang, Yunda
Ferrari, Guido
Alter, Galit
Forthal, Donald N
Kappes, John C
Lewis, George K
Love, J Christopher
Borate, Bhavesh
Harris, Linda
Greene, Kelli
Gao, Hongmei
Phan, Tran B
Landucci, Gary
Goods, Brittany A
Dowell, Karen G
Cheng, Hao D
Bailey-Kellogg, Chris
Montefiori, David C
Ackerman, Margaret E
author2 Massachusetts Institute of Technology. Department of Chemical Engineering
author_facet Massachusetts Institute of Technology. Department of Chemical Engineering
Huang, Yunda
Ferrari, Guido
Alter, Galit
Forthal, Donald N
Kappes, John C
Lewis, George K
Love, J Christopher
Borate, Bhavesh
Harris, Linda
Greene, Kelli
Gao, Hongmei
Phan, Tran B
Landucci, Gary
Goods, Brittany A
Dowell, Karen G
Cheng, Hao D
Bailey-Kellogg, Chris
Montefiori, David C
Ackerman, Margaret E
author_sort Huang, Yunda
collection MIT
description 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.
first_indexed 2024-09-23T11:46:34Z
format Article
id mit-1721.1/133926
institution Massachusetts Institute of Technology
language English
last_indexed 2024-09-23T11:46:34Z
publishDate 2021
publisher The American Association of Immunologists
record_format dspace
spelling mit-1721.1/1339262023-09-25T20:58:46Z Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects Huang, Yunda Ferrari, Guido Alter, Galit Forthal, Donald N Kappes, John C Lewis, George K Love, J Christopher Borate, Bhavesh Harris, Linda Greene, Kelli Gao, Hongmei Phan, Tran B Landucci, Gary Goods, Brittany A Dowell, Karen G Cheng, Hao D Bailey-Kellogg, Chris Montefiori, David C Ackerman, Margaret E Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Biological Engineering 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. 2021-10-27T19:57:14Z 2021-10-27T19:57:14Z 2016 2019-09-09T16:10:28Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133926 Huang, Y., et al. "Diversity of Antiviral Igg Effector Activities Observed in Hiv-Infected and Vaccinated Subjects." J Immunol 197 12 (2016): 4603-12. en 10.4049/JIMMUNOL.1601197 Journal of immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf The American Association of Immunologists PMC
spellingShingle Huang, Yunda
Ferrari, Guido
Alter, Galit
Forthal, Donald N
Kappes, John C
Lewis, George K
Love, J Christopher
Borate, Bhavesh
Harris, Linda
Greene, Kelli
Gao, Hongmei
Phan, Tran B
Landucci, Gary
Goods, Brittany A
Dowell, Karen G
Cheng, Hao D
Bailey-Kellogg, Chris
Montefiori, David C
Ackerman, Margaret E
Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
title Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
title_full Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
title_fullStr Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
title_full_unstemmed Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
title_short Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
title_sort diversity of antiviral igg effector activities observed in hiv infected and vaccinated subjects
url https://hdl.handle.net/1721.1/133926
work_keys_str_mv AT huangyunda diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT ferrariguido diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT altergalit diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT forthaldonaldn diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT kappesjohnc diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT lewisgeorgek diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT lovejchristopher diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT boratebhavesh diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT harrislinda diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT greenekelli diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT gaohongmei diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT phantranb diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT landuccigary diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT goodsbrittanya diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT dowellkareng diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT chenghaod diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT baileykelloggchris diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT montefioridavidc diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects
AT ackermanmargarete diversityofantiviraliggeffectoractivitiesobservedinhivinfectedandvaccinatedsubjects