Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features
Abstract 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. T...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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BioMed Central
2021
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| Online Access: | https://hdl.handle.net/1721.1/136961 |
| _version_ | 1826215280576036864 |
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| author | Cheng, Hao D. Dowell, Karen G. Bailey-Kellogg, Chris Goods, Brittany A. Love, J. C. Ferrari, Guido Alter, Galit Gach, Johannes Forthal, Donald N. Lewis, George K. Greene, Kelli Gao, Hongmei Montefiori, David C. Ackerman, Margaret E. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Cheng, Hao D. Dowell, Karen G. Bailey-Kellogg, Chris Goods, Brittany A. Love, J. C. 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 | MIT |
| description | Abstract
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. |
| first_indexed | 2024-09-23T16:21:40Z |
| format | Article |
| id | mit-1721.1/136961 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:21:40Z |
| publishDate | 2021 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1369612023-01-20T16:42:55Z 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. C. Ferrari, Guido Alter, Galit Gach, Johannes Forthal, Donald N. Lewis, George K. Greene, Kelli Gao, Hongmei Montefiori, David C. Ackerman, Margaret E. Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT Ragon Institute of MGH, MIT and Harvard Abstract 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. 2021-11-01T15:31:54Z 2021-11-01T15:31:54Z 2021-10-30 2021-10-31T04:19:47Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136961 Retrovirology. 2021 Oct 30;18(1):35 PUBLISHER_CC en https://doi.org/10.1186/s12977-021-00579-9 Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central |
| spellingShingle | Cheng, Hao D. Dowell, Karen G. Bailey-Kellogg, Chris Goods, Brittany A. Love, J. C. 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 |
| url | https://hdl.handle.net/1721.1/136961 |
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