Role of prior HPV infection and CD4 T-cell count in modulating cellular immune responses to a three-dose nonavalent HPV vaccine schedule in PWH receiving ART

Background: Most studies on HPV vaccination have focused on the antibody response and on bivalent and quadrivalent vaccines. For these reasons, an evaluation of T-cell responses in PWH on effective ART to the Gardasil 9® vaccine according to prior HPV infection and baseline CD4 T-cell count was performed. Methods: We prospectively enrolled PWH on effective ART. T-cell responses were assessed by flow cytometry at pre-vaccination (T0), on the same day of the third dose (T1) and 6 months after the third dose (T2) after stimulation with a pool of HPV16 and HPV18 L1 peptide libraries. An evaluation of IFN-γ in supernatants was also carried out. Baseline CD4 T-cell count was defined at the first dose. Results: An increase in the percentage of responding and polyfunctional T-cells was found in both HPV − and HPV + groups, with no significant differences between them at any time point. When the population was stratified according to baseline CD4 T-cell count, an increase was found only in > 500 cells/μL group for both the responding and polyfunctional T-cells. Furthermore, a higher frequency of responding CD4 T-cells at T1 (p = 0.0049), a higher frequency of responding CD8 T-cells at T1 and T2 (p = 0.05 and p = 0.02, respectively), a higher frequency of polyfunctional CD4 T-cells at T1 (p = 0.0242) and a higher frequency of polyfunctional CD8 T-cells at T2 (p = 0.02) were found in > 500 cells/μL group than in their relative counterpart. The analysis of the estimated change from T0 revealed no statistically significant differences between PWH with or without prior HPV infection, whereas significant associations between higher CD4 counts and improved immune responses were found. Conclusions: Our study revealed a coordinated T-cell response against HPV16 and 18 after Gardasil9® vaccine in PWH, including those with a history of HPV infection. PWH with a lower CD4 T-cell count remains a group who may not mount a fully protective immune response and, therefore, may require additional protection or ad hoc vaccination strategies. These data reinforce the key role of basal CD4 level in modulating the immune response over time, while prior HPV infection did not significantly affect the rate and quality of the response.