Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression.
HIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012739 |
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| author | Marloes Grobben Margreet Bakker Angela I Schriek Liesbeth J J Levels Jeffrey C Umotoy Khadija Tejjani Mariëlle J van Breemen Ryan N Lin Steven W de Taeye Gabriel Ozorowski Neeltje A Kootstra Andrew B Ward Stephen J Kent P Mark Hogarth Bruce D Wines Rogier W Sanders Amy W Chung Marit J van Gils |
| author_facet | Marloes Grobben Margreet Bakker Angela I Schriek Liesbeth J J Levels Jeffrey C Umotoy Khadija Tejjani Mariëlle J van Breemen Ryan N Lin Steven W de Taeye Gabriel Ozorowski Neeltje A Kootstra Andrew B Ward Stephen J Kent P Mark Hogarth Bruce D Wines Rogier W Sanders Amy W Chung Marit J van Gils |
| author_sort | Marloes Grobben |
| collection | DOAJ |
| description | HIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial effects of antibodies during HIV-1 infection are poorly understood. To identify a specific profile of antibody features associated with delayed disease progression, we studied antibody polyfunctionality during untreated HIV-1 infection in the well-documented Amsterdam Cohort Studies. Serum samples were analyzed from untreated individuals with HIV-1 at approximately 6 months (n = 166) and 3 years (n = 382) post-seroconversion (post-SC). A Luminex antibody Fc array was used to profile 15 different Fc features for serum antibodies against 20 different HIV-1 envelope glycoprotein antigens and the resulting data was also compared with data on neutralization breadth. We found that high HIV-1 specific IgG1 levels and low IgG2 and IgG4 levels at 3 years post-SC were associated with delayed disease progression. Moreover, delayed disease progression was associated with a broad and polyfunctional antibody response. Specifically, the capacity to interact with all Fc γ receptors (FcγRs) and C1q, and in particular with FcγRIIa, correlated positively with delayed disease progression. There were strong correlations between antibody Fc features and neutralization breadth and several antibody features that were associated with delayed disease progression were also associated with the development of broad and potent antibody neutralization. In summary, we identified a strong association between broad, polyfunctional antibodies and delayed disease progression. These findings contribute new information for the fight against HIV-1, especially for new antibody-based therapy and cure strategies. |
| format | Article |
| id | doaj-art-b7fc8d66d7814d5bb991e391aaec82f3 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-b7fc8d66d7814d5bb991e391aaec82f32025-08-20T02:23:15ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-12-012012e101273910.1371/journal.ppat.1012739Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression.Marloes GrobbenMargreet BakkerAngela I SchriekLiesbeth J J LevelsJeffrey C UmotoyKhadija TejjaniMariëlle J van BreemenRyan N LinSteven W de TaeyeGabriel OzorowskiNeeltje A KootstraAndrew B WardStephen J KentP Mark HogarthBruce D WinesRogier W SandersAmy W ChungMarit J van GilsHIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial effects of antibodies during HIV-1 infection are poorly understood. To identify a specific profile of antibody features associated with delayed disease progression, we studied antibody polyfunctionality during untreated HIV-1 infection in the well-documented Amsterdam Cohort Studies. Serum samples were analyzed from untreated individuals with HIV-1 at approximately 6 months (n = 166) and 3 years (n = 382) post-seroconversion (post-SC). A Luminex antibody Fc array was used to profile 15 different Fc features for serum antibodies against 20 different HIV-1 envelope glycoprotein antigens and the resulting data was also compared with data on neutralization breadth. We found that high HIV-1 specific IgG1 levels and low IgG2 and IgG4 levels at 3 years post-SC were associated with delayed disease progression. Moreover, delayed disease progression was associated with a broad and polyfunctional antibody response. Specifically, the capacity to interact with all Fc γ receptors (FcγRs) and C1q, and in particular with FcγRIIa, correlated positively with delayed disease progression. There were strong correlations between antibody Fc features and neutralization breadth and several antibody features that were associated with delayed disease progression were also associated with the development of broad and potent antibody neutralization. In summary, we identified a strong association between broad, polyfunctional antibodies and delayed disease progression. These findings contribute new information for the fight against HIV-1, especially for new antibody-based therapy and cure strategies.https://doi.org/10.1371/journal.ppat.1012739 |
| spellingShingle | Marloes Grobben Margreet Bakker Angela I Schriek Liesbeth J J Levels Jeffrey C Umotoy Khadija Tejjani Mariëlle J van Breemen Ryan N Lin Steven W de Taeye Gabriel Ozorowski Neeltje A Kootstra Andrew B Ward Stephen J Kent P Mark Hogarth Bruce D Wines Rogier W Sanders Amy W Chung Marit J van Gils Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression. PLoS Pathogens |
| title | Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression. |
| title_full | Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression. |
| title_fullStr | Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression. |
| title_full_unstemmed | Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression. |
| title_short | Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression. |
| title_sort | polyfunctionality and breadth of hiv 1 antibodies are associated with delayed disease progression |
| url | https://doi.org/10.1371/journal.ppat.1012739 |
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