Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity
| Autor: | Amy W. Chung, Jenniffer M. Mabuka, Yathisha Ramlakhan, Philip J. R. Goulder, Bongiwe Ndlovu, Musie Ghebremichael, Bruce D. Walker, Hannah Robinson, Galit Alter, Anna Licht, Thumbi Ndung'u, Tarylee Reddy |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genotype viruses Immunology HIV Core Protein p24 HIV Infections Receptors Fc Human leukocyte antigen HIV Antibodies Cell Degranulation Immunoglobulin G Cohort Studies 03 medical and health sciences 0302 clinical medicine Immune system Phagocytosis Humans Immunology and Allergy Natural killer cell degranulation Antibody-dependent cell-mediated cytotoxicity biology Antibody-Dependent Cell Cytotoxicity virus diseases Viral Load Killer Cells Natural 030104 developmental biology Infectious Diseases Humoral immunity HIV-1 biology.protein Antibody Viral load 030215 immunology |
| Zdroj: | AIDS |
| ISSN: | 0269-9370 |
| Popis: | OBJECTIVE: Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. DESIGN: Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naive participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential. METHOD: Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated natural killer cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), respectively. RESULTS: p24 IgG1 was the only subclass associated with viral control (P = 0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in patients with elevated Gag-specific T-cell responses, these levels remained an independent predictor of low-viral loads (P = 0.04) and high CD4+ cell counts (P = 0.004) after adjusting for Gag-specific T-cell responses and for protective HLA class I alleles. CONCLUSION: p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection. |
| Databáze: | OpenAIRE |
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