Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity

Chung, Amy W.; Mabuka, Jenniffer M.; Ndlovu, Bongiwe; Licht, Anna; Robinson, Hannah; Ramlakhan, Yathisha; Ghebremichael, Musie; Reddy, Tarylee; Goulder, Philip; Walker, Bruce D.; Ndung’u, Thumbi; Alter, Galit

doi:10.1097/qad.0000000000001812

Cited by 24 publications

(31 citation statements)

References 56 publications

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“…CD8 T cells are important for virus control, and robust IL-21-mediated Tfh cell help to CD8 T cells improves CD8 T cell cytolytic activity (37), but we observed no correlations between the frequencies of IFN-␥-positive CD8 T cells and lower set point viral loads among our study participants. Additionally, a paper from our group showed that the association between Gag p24 IgG and viral control was still maintained even after controlling for Gag-specific CD4 and CD8 T cell responses, suggesting a CD8 T cell-independent antiviral mechanism of these antibodies (50).…”

Section: Discussionmentioning

confidence: 86%

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: 86%

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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“…[ 9 , 22 , 30 , 34 , 35 ] Suppressive ART might also have an impact on antibody responses to HIV infection. [ 36 , 37 ] Some studies showed a weak antibody response in a proportion of patients with early ART and fewer patients starting ART in chronic HIV infection. [ 38 ] In addition, patients with long-term suppressive ART still had continuous antigenic stimulation and lead to the evolution of HIV-specific antibody.…”

Section: Discussionmentioning

confidence: 99%

Treatment outcomes and HIV drug resistance of patients switching to second-line regimens after long-term first-line antiretroviral therapy

Cao

et al. 2018

Medicine

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“…Multiple studies have associated HIV-specific IgG3 with viral control and enhanced Fc-functions (172,178,188,189). IgG1 and IgG2 against internal HIV-1 p24 protein have also associated with viral control though the mechanisms are still not understood (190,191). As with active TB, IgG1, and IgG3 subclass predominates in HIV-1, however the connection between these specific IgG subclasses and inflammation in the context of HIV-1 is yet to be investigated.…”

Section: Antibody Isotypes and Subclasses In Hiv-1mentioning

confidence: 99%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with proinflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

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Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity

Cited by 24 publications

References 56 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

Treatment outcomes and HIV drug resistance of patients switching to second-line regimens after long-term first-line antiretroviral therapy

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

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