Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features
© 2021 Bartsch et al. Plasma viremia reoccurs in most HIV-infected individuals once antiretro-viral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virologi...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2021
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| Online Access: | https://hdl.handle.net/1721.1/135538 |
| _version_ | 1811087966899011584 |
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| author | Bartsch, Yannic C Loos, Carolin Rossignol, Evan Fajnzylber, Jesse M Yuan, Dansu Avihingsanon, Anchalee Ubolyam, Sasiwimol Jupimai, Thidarat Hirschel, Bernard Ananworanich, Jintanat Lauffenburger, Douglas A Li, Jonathan Z Alter, Galit Julg, Boris |
| author2 | Ragon Institute of MGH, MIT and Harvard |
| author_facet | Ragon Institute of MGH, MIT and Harvard Bartsch, Yannic C Loos, Carolin Rossignol, Evan Fajnzylber, Jesse M Yuan, Dansu Avihingsanon, Anchalee Ubolyam, Sasiwimol Jupimai, Thidarat Hirschel, Bernard Ananworanich, Jintanat Lauffenburger, Douglas A Li, Jonathan Z Alter, Galit Julg, Boris |
| author_sort | Bartsch, Yannic C |
| collection | MIT |
| description | © 2021 Bartsch et al. Plasma viremia reoccurs in most HIV-infected individuals once antiretro-viral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virological and immunological factors have been suggested. Standard clinical measures, like CD4 T-cell counts and plasma HIV RNA levels, how-ever, are poor predictive markers. Antibody features, including Fc functionality and Fc glycosylation have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we analyzed HIV-specific antibody quantities and qualitative differences like antibody-mediated functions, Fc gamma receptor (FcγR) binding, and IgG Fc glycosylation as well as cytokine profiles and cellular HIV DNA and RNA levels in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders (≤4 weeks versus >4 weeks) and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. Specifically, individuals with early viral rebound exhibited higher levels of total HIV-specific IgGs carrying inflammatory Fc glycans, while delayed rebounders showed an enrichment of highly functional antibodies. Overall, only four features, including enhanced antibody-mediated NK cell activation in delayed rebounders, were necessary to discriminate the groups. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future ATI studies. IMPORTANCE Plasma viremia reoccurs in most HIV-infected individuals once antiretro-viral therapy is interrupted, and interindividual differences in the kinetics of viral rebound have been associated with virological and immunological factors. Antibody features, including Fc functionality and Fc glycosylation, have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we systematically analyzed HIV-specific antibody quantities and qualitative differences in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future HIV eradication studies. |
| first_indexed | 2024-09-23T13:54:40Z |
| format | Article |
| id | mit-1721.1/135538 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:54:40Z |
| publishDate | 2021 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | mit-1721.1/1355382023-09-12T20:16:37Z Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features Bartsch, Yannic C Loos, Carolin Rossignol, Evan Fajnzylber, Jesse M Yuan, Dansu Avihingsanon, Anchalee Ubolyam, Sasiwimol Jupimai, Thidarat Hirschel, Bernard Ananworanich, Jintanat Lauffenburger, Douglas A Li, Jonathan Z Alter, Galit Julg, Boris Ragon Institute of MGH, MIT and Harvard Massachusetts Institute of Technology. Department of Biological Engineering © 2021 Bartsch et al. Plasma viremia reoccurs in most HIV-infected individuals once antiretro-viral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virological and immunological factors have been suggested. Standard clinical measures, like CD4 T-cell counts and plasma HIV RNA levels, how-ever, are poor predictive markers. Antibody features, including Fc functionality and Fc glycosylation have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we analyzed HIV-specific antibody quantities and qualitative differences like antibody-mediated functions, Fc gamma receptor (FcγR) binding, and IgG Fc glycosylation as well as cytokine profiles and cellular HIV DNA and RNA levels in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders (≤4 weeks versus >4 weeks) and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. Specifically, individuals with early viral rebound exhibited higher levels of total HIV-specific IgGs carrying inflammatory Fc glycans, while delayed rebounders showed an enrichment of highly functional antibodies. Overall, only four features, including enhanced antibody-mediated NK cell activation in delayed rebounders, were necessary to discriminate the groups. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future ATI studies. IMPORTANCE Plasma viremia reoccurs in most HIV-infected individuals once antiretro-viral therapy is interrupted, and interindividual differences in the kinetics of viral rebound have been associated with virological and immunological factors. Antibody features, including Fc functionality and Fc glycosylation, have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we systematically analyzed HIV-specific antibody quantities and qualitative differences in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future HIV eradication studies. 2021-10-27T20:23:53Z 2021-10-27T20:23:53Z 2021 2021-09-07T16:33:41Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135538 en 10.1128/MBIO.00170-21 mBio [21507511] Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Microbiology mBio |
| spellingShingle | Bartsch, Yannic C Loos, Carolin Rossignol, Evan Fajnzylber, Jesse M Yuan, Dansu Avihingsanon, Anchalee Ubolyam, Sasiwimol Jupimai, Thidarat Hirschel, Bernard Ananworanich, Jintanat Lauffenburger, Douglas A Li, Jonathan Z Alter, Galit Julg, Boris Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features |
| title | Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features |
| title_full | Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features |
| title_fullStr | Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features |
| title_full_unstemmed | Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features |
| title_short | Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features |
| title_sort | viral rebound kinetics correlate with distinct hiv antibody features |
| url | https://hdl.handle.net/1721.1/135538 |
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