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Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features

BACKGROUND: The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mechanism(s) by which immunoglobulin G (IgG) Fc...

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Autores principales: Cheng, Hao D., Dowell, Karen G., Bailey-Kellogg, Chris, Goods, Brittany A., Love, J. Christopher, Ferrari, Guido, Alter, Galit, Gach, Johannes, Forthal, Donald N., Lewis, George K., Greene, Kelli, Gao, Hongmei, Montefiori, David C., Ackerman, Margaret E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557579/
https://www.ncbi.nlm.nih.gov/pubmed/34717659
http://dx.doi.org/10.1186/s12977-021-00579-9
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author Cheng, Hao D.
Dowell, Karen G.
Bailey-Kellogg, Chris
Goods, Brittany A.
Love, J. Christopher
Ferrari, Guido
Alter, Galit
Gach, Johannes
Forthal, Donald N.
Lewis, George K.
Greene, Kelli
Gao, Hongmei
Montefiori, David C.
Ackerman, Margaret E.
author_facet Cheng, Hao D.
Dowell, Karen G.
Bailey-Kellogg, Chris
Goods, Brittany A.
Love, J. Christopher
Ferrari, Guido
Alter, Galit
Gach, Johannes
Forthal, Donald N.
Lewis, George K.
Greene, Kelli
Gao, Hongmei
Montefiori, David C.
Ackerman, Margaret E.
author_sort Cheng, Hao D.
collection PubMed
description BACKGROUND: The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mechanism(s) by which immunoglobulin G (IgG) Fc domain and cognate receptors may afford protection are poorly understood, however, in the context of HIV/SHIV infections. Many different in vitro assays have been developed and utilized to measure effector functions, but the extent to which these assays capture distinct antibody activities has not been fully elucidated. RESULTS: In this study, six Fc-mediated effector function assays and two biophysical antibody profiling assays were performed on a common set of samples from HIV-1 infected and vaccinated subjects. Biophysical antibody profiles supported robust prediction of diverse IgG effector functions across distinct Fc-mediated effector function assays. While a number of assays showed correlated activities, supervised machine learning models indicated unique antibody features as primary contributing factors to the associated effector functions. Additional experiments established the mechanistic relevance of relationships discovered using this unbiased approach. CONCLUSIONS: In sum, this study provides better resolution on the diversity and complexity of effector function assays, offering a clearer perspective into this family of antibody mechanisms of action to inform future HIV-1 treatment and vaccination strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12977-021-00579-9.
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spelling pubmed-85575792021-11-03 Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features Cheng, Hao D. Dowell, Karen G. Bailey-Kellogg, Chris Goods, Brittany A. Love, J. Christopher Ferrari, Guido Alter, Galit Gach, Johannes Forthal, Donald N. Lewis, George K. Greene, Kelli Gao, Hongmei Montefiori, David C. Ackerman, Margaret E. Retrovirology Research BACKGROUND: The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mechanism(s) by which immunoglobulin G (IgG) Fc domain and cognate receptors may afford protection are poorly understood, however, in the context of HIV/SHIV infections. Many different in vitro assays have been developed and utilized to measure effector functions, but the extent to which these assays capture distinct antibody activities has not been fully elucidated. RESULTS: In this study, six Fc-mediated effector function assays and two biophysical antibody profiling assays were performed on a common set of samples from HIV-1 infected and vaccinated subjects. Biophysical antibody profiles supported robust prediction of diverse IgG effector functions across distinct Fc-mediated effector function assays. While a number of assays showed correlated activities, supervised machine learning models indicated unique antibody features as primary contributing factors to the associated effector functions. Additional experiments established the mechanistic relevance of relationships discovered using this unbiased approach. CONCLUSIONS: In sum, this study provides better resolution on the diversity and complexity of effector function assays, offering a clearer perspective into this family of antibody mechanisms of action to inform future HIV-1 treatment and vaccination strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12977-021-00579-9. BioMed Central 2021-10-30 /pmc/articles/PMC8557579/ /pubmed/34717659 http://dx.doi.org/10.1186/s12977-021-00579-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cheng, Hao D.
Dowell, Karen G.
Bailey-Kellogg, Chris
Goods, Brittany A.
Love, J. Christopher
Ferrari, Guido
Alter, Galit
Gach, Johannes
Forthal, Donald N.
Lewis, George K.
Greene, Kelli
Gao, Hongmei
Montefiori, David C.
Ackerman, Margaret E.
Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features
title Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features
title_full Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features
title_fullStr Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features
title_full_unstemmed Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features
title_short Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features
title_sort diverse antiviral igg effector activities are predicted by unique biophysical antibody features
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557579/
https://www.ncbi.nlm.nih.gov/pubmed/34717659
http://dx.doi.org/10.1186/s12977-021-00579-9
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