Responses to Quadrivalent Influenza Vaccine Reveal Distinct Circulating CD4+CXCR5+ T Cell Subsets in Men Living with HIV

T cell help for B cells may be perturbed in people living with HIV (PLWH), even when HIV is suppressed, as evidenced by reports of suboptimal responses to influenza vaccination. We investigated cT_FH responses to the 2017–18 inactivated quadrivalent influenza vaccine (QIV) in men living with antiretroviral therapy (ART)-suppressed HIV infection who were treated in the early or chronic phase of infection, and control subjects. Here we show that seroprotective antibody responses in serum and oral fluid correlated with cT_FH activation and were equivalent in all three groups, irrespective of when ART was started. These responses were attenuated in those reporting immunisation with influenza vaccine in the preceding three years, independent of HIV infection. Measurement of influenza-specific IgG in oral fluid was closely correlated with haemagglutination inhibition titre. T-SNE and two-dimensional analysis revealed a subset of CD4⁺CXCR3⁺CXCR5⁺ cT_FH activated at one week after vaccination. This was distinguishable from cTFH not activated by vaccination, and a rare, effector memory CD4⁺CXCR5^hiCD32^hi T cell subset. The data support the use of QIV for immunisation of PLWH, reveal distinct circulating CD4⁺CXCR5⁺ T cell subsets and demonstrate oral fluid sampling for influenza-specific IgG is an alternative to phlebotomy.