Association of HIV-1 Gag-Specific IgG Antibodies With Natural Control of HIV-1 Infection in Individuals Not Carrying HLA-B*57:01 Is Only Observed in Viremic Controllers

Tjiam, M. Christian; Morshidi, Mazmah A.; Sariputra, Lucy; Martin, Jeffrey N.; Deeks, Steven G.; Tan, Dino B.A.; Lee, Silvia; Fernández, Sonia; French, Martyn A.

doi:10.1097/qai.0000000000001477

Cited by 7 publications

(11 citation statements)

References 23 publications

(29 reference statements)

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“…Fc effector functions, like antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), have been described to be important for virus control, and these functions are mostly attributed to Env-specific IgG antibodies (41,42). Additionally, studies investigating the mechanisms for virus suppression by Gag-specific antibodies have described the ability of Gag-specific antibodies to opsonize antigens and recruit conventional or plasmacytoid dendritic cells to phagocytose antibody-coated antigens (43)(44)(45). These opsonophagocytic IgG responses were associated with lower plasma HIV RNA levels (43,46), thus highlighting another potential mechanism of virus control.…”

Section: Discussionmentioning

confidence: 99%

Frequencies of Circulating Th1-Biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-Specific Antibody Responses and Lower Set Point Viral Load

Baiyegunhi

Ndlovu

Ogunshola

et al. 2018

J Virol

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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 ( = 0.02) and Tfh2 ( < 0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (which shares both Tfh1 and Tfh17 properties) ( = 0.01) and Tfh17 ( < 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 ( = 0.03, Spearman rho [] = -60) and were predictive of p24-specific plasma IgG titers at 1 year of infection ( = 0.003, = 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. 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 Tfh1 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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Section: Discussionmentioning

confidence: 99%

Frequencies of Circulating Th1-Biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-Specific Antibody Responses and Lower Set Point Viral Load

Baiyegunhi

Ndlovu

Ogunshola

et al. 2018

J Virol

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“…Interesting, HIV controllers not carrying a protective HLA-B allele had significantly higher levels of IgG2 against Gag protein and IgG1 against p32, whereas IgG1 levels were significantly higher in FcgRIIa-binding immune complexes from HIV non-controllers than in HIV controllers ( 127 ). Moreover, in the same group, the association between HIV-1 p24-specific IgG Abs and natural control of HIV-1 infection in individuals not carrying HLA-B * 5701 was only observed in HIV controllers, but not in elite controllers or non-controllers (>10,000 copies/mL) ( 128 ). HIV-1 p24-specific IgG Abs exhibited higher plasmacytoid dendritic cell (pDC)-reactive opsonophagocytosis in HIV controllers and elite controllers than in non-controllers ( 129 ).…”

Section: Resultsmentioning

confidence: 99%

Association of Diverse Genotypes and Phenotypes of Immune Cells and Immunoglobulins With the Course of HIV-1 Infection

Liu

Gorny

2018

Front. Immunol.

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Disease progression among HIV-1–infected individuals varies widely, but the mechanisms underlying this variability remains unknown. Distinct disease outcomes are the consequences of many factors working in concert, including innate and adaptive immune responses, cell-mediated and humoral immunity, and both genetic and phenotypic factors. Current data suggest that these multifaceted aspects in infected individuals should be considered as a whole, rather than as separate unique elements, and that analyses must be performed in greater detail in order to meet the requirements of personalized medicine and guide optimal vaccine design. However, the wide adoption of antiretroviral therapy (ART) influences the implementation of systematic analyses of the HIV-1–infected population. Consequently, fewer data will be available for acquisition in the future, preventing the comprehensive investigations required to elucidate the underpinnings of variability in disease outcome. This review seeks to recapitulate the distinct genotypic and phenotypic features of the immune system, focusing in particular on comparing the surface proteins of immune cells among individuals with different HIV infection outcomes.

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“…V1V2-gp70 loop specific antibodies identified as immune correlates of reduced risk of infection in the RV144 trial vaccinees (17,18,47,48) elicited ADCC, virion capture and limited tier 1 virus neutralization (49)(50)(51). P24-specific IgG1 responses were associated with reduced viral loads (10,52,53) and improved CD4 + T cell counts in HIV-1 subtype C infected participants (9). The direct associations between V1V2-gp70-specific ADNP, p24-specific ADCC and CD4 + T cell counts in the plasma of HIV infected women from the tenofovir arm suggest that polyfunctional antibodies may be needed to synergise nNAb activities to not only control viral load (44) and impact HIV disease progression but also to confer protection.…”

Section: Discussionmentioning

confidence: 99%

Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women

Mabuka

Sivro

et al. 2020

Front. Immunol.

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Association of HIV-1 Gag-Specific IgG Antibodies With Natural Control of HIV-1 Infection in Individuals Not Carrying HLA-B*57:01 Is Only Observed in Viremic Controllers

Cited by 7 publications

References 23 publications

Frequencies of Circulating Th1-Biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-Specific Antibody Responses and Lower Set Point Viral Load

Frequencies of Circulating Th1-Biased T Follicular Helper Cells in Acute HIV-1 Infection Correlate with the Development of HIV-Specific Antibody Responses and Lower Set Point Viral Load

Association of Diverse Genotypes and Phenotypes of Immune Cells and Immunoglobulins With the Course of HIV-1 Infection

Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women

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