Evaluating the Role of Early HIV-Specific T and B Cell Phenotypes and Interaction in Determining Downstream Antibody Function in HIV Infection

Oyaro, Nyakundi Ian (2021). Evaluating the Role of Early HIV-Specific T and B Cell Phenotypes and Interaction in Determining Downstream Antibody Function in HIV Infection. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.000132a6

Abstract

There is limited knowledge on how to induce potent antiviral antibodies in HIV vaccine strategies. Studies of HIV infected individuals who develop potent anti-HIV antibodies could inform rational vaccine immunogen design approaches. Phenotypic characteristics of T and B cells, as well as interactions between these cells early in infection may affect the quality of antiviral antibodies. This study investigated the impact of the general and HIV-specific T and B cell phenotypes and interactions in early HIV infection on subsequent anti-HIV antibody quality.

Using a cohort of 53 antiretroviral-naive HIV-infected adults that were longitudinally followed for approximately 48 months, the general and HIV-specific T and B cell subsets, as well as plasma CXCL13 and B cell-activating factor levels, as proxy for germinal centre activities, were determined in early infection and their association with subsequent development of antibody levels and their neutralising and Fc-mediated functions assessed.

Atypical B cells were elevated in HIV, (20% [IQR, 12.15-29.55] versus 5.4% [IQR, 3.45-6.67] in HIV-naive donors, p<0.0001), whereas CD4+ T cells were depleted (41.6% [IQR, 32.2-53.1] versus 50.4% [IQR, 48.1-55.65], p=0.004). HIV-specific B and T-follicular helper (Tfh) cells were detected in infected individuals, 0.58% (IQR, 0.41%-0.9%) and 0.54% (IQR, 0.3-0.83), respectively. Antibody neutralization breadth was detected in 28.3% of the participants, while Fc-mediated functions were common, with 15.1% of the individuals showing quality Fc-polyfunctionality over time.

The Tfh subset, ICOS+ PD-1+ CXCR5+ CD4+, was associated with subsequent higher IgG titres (rho=0.3135, p=0.025), while HIV-specific Tfh cells predicted interferon-gamma release by natural killer cells (rho=0.3314, p=0.018). Activated B cells were positively associated with higher IgG₁ levels (rho=0.4285, p=0.0014). Similarly, HIV-specific B cells and CXCL13 levels were associated with higher IgG3, (rho=0.3, p=0.029), and IgG levels (rho=0.37, p=0.006), respectively.

The data suggest that early T and B cell features can be predictive of downstream antibody functions and levels. Immunological signatures identified early in HIV infection could be useful in shepherding desired antibody responses.

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