期刊
JOURNAL OF VIROLOGY
卷 92, 期 15, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00659-18
关键词
HIV; T follicular helper cells; nonneutralizing antibodies; Gag p24 IgG; Gag p24 IgG antibodies; circulating Tfh cells
类别
资金
- HHMI international research scholar award [55008743]
- U.S. National Institutes of Health [R37 AI67073]
- Dan and Marjorie Sullivan research scholar award [224910]
- National Research Foundation (NRF)
- South African Research Chairs Initiative
- Mark and Lisa Schwartz Foundation
- Bill & Melinda Gates Foundation
- International AIDS Vaccine Initiative (IAVI) [UKZNRSA1001]
- Victor Daitz Foundation
- Gilead Sciences Incorporated
- Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE)
- DELTAS Africa Initiative [DEL-15-006]
- African Academy of Sciences (AAS) Alliance for Accelerating Excellence in Science in Africa (AESA)
- New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency)
- Wellcome Trust [107752/Z/15/Z]
- UK government
Despite decades of focused research, the field has yet to develop a prophylactic vaccine for HIV-1 infection. In the RV144 vaccine trial, nonneutralizing antibody responses were identified as a correlate for prevention of HIV acquisition. However, factors that predict the development of such antibodies are not fully elucidated. We sought to define the contribution of circulating T follicular helper (cTfh) subsets to the development of nonneutralizing antibodies in HIV-1 clade C infection. Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-gp41, -gp120, -p24, and -p17 antibodies were screened using a customized multivariate Luminex assay. Phenotypic and functional characterizations of cTfh cells were performed using HLA class II tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C infection skewed the differentiation of functional cTfh subsets toward increased Tfh1 (P = 0.02) and Tfh2 (P < 0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (which shares both Tfh1 and Tfh17 properties) (P = 0.01) and Tfh17 (P < 0.0001) subsets, compared to the subsets found in HIV-negative subjects. Interestingly, the frequencies of Tfh1 cells during acute infection (5.0 to 8.0 weeks postinfection) correlated negatively with the set point viral load (P = 0.03, Spearman rho [r] = -60) and were predictive of p24-specific plasma IgG titers at 1 year of infection (P = 0.003, r = 0.85). Taken together, our results suggest that the circulating Tfh1 subset plays an important role in the development of anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. These results have implications for vaccine studies aimed at inducing long-lasting anti-HIV antibody responses. IMPORTANCE The HIV epidemic in southern Africa accounts for almost half of the global HIV burden, with HIV-1 clade C being the predominant strain. It is therefore important to define immune correlates of clade C HIV control that might have implications for vaccine design in this region. T follicular helper (Tfh) cells are critical for the development of HIV-specific antibody responses and could play a role in viral control. Here we showed that the early induction of circulating Tfh 1 cells during acute infection correlated positively with the magnitude of p24-specific IgG and was associated with a lower set point viral load. This study highlights a key Tfh cell subset that could limit HIV replication by enhancing antibody generation. This study underscores the importance of circulating Tfh cells in promoting nonneutralizing antibodies during HIV-1 infection.
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