IL-2-mediated CD4 T-cell activation correlates highly with effective
serological and T-cell responses to SARS-CoV-2 vaccination in people
living with HIV (PLWH)
Abstract
People living with HIV (PLWH) despite having appreciable depletion of
CD4 + T-cell show a good SARS-CoV-2 vaccination
response. The underlying mechanism(s) are currently not understood. We
studied serological and polyfunctional T-cell responses in PLWH
receiving anti-retroviral therapy stratified on CD4 +
counts as PLWH-high (CD4 ≥500 cells/μL) and PLWH-low (<500
cells/μL). Responses were assessed longitudinally before the first
vaccination (T0), 1-month after the first dose (T1), and 3-months (T2),
and 6-months (T3) after the second dose. Expectedly, both PLWH-high and
-low groups developed similar serological responses after T2, which were
also non-significantly different to age and vaccination-matched
HIV-negative controls at T3. The IgG titers were also protective showing
a good correlation with ACE2-neutralizations (R=0.628, P=0.005). While
no difference at T3 was observed between PLWH and controls in activated
CD4 +CD154 + and CD4
+ memory T-cells, spike-specific CD4
+ polyfunctional cytokine expression analysis showed
that PLWH preferentially express IL-2 (P<0.001) and controls,
IFN-γ (P=0.017). CD4 + T-cell counts negatively
correlated with IL-2-expressing CD4 + T-cells
including CD4 + memory T-cells (Spearman ρ: -0.85
and -0.80, respectively; P<0.001). Our results suggest that the
durable serological and CD4 + T-cell responses
developing in vaccinated PLWH are associated with IL-2-mediated CD4
+ T-cell activation that likely compensates for CD4
+ T-cell depletion in PLWH.