Long-Term Follow-Up of T Cell Immunity Against Orthopoxviruses in People Living with HIV After Vaccination and Natural Monkeypox Virus Infection

Background/Objectives: After the 2022 mpox outbreak also outside Africa, risk groups including people living with HIV (PLWH) were vaccinated with the Modified Vaccinia Ankara–Bavarian Nordic vaccine (MVA-BN). Previous data on PLWH showed that two vaccinations induced specific T cell responses in 64% of the patients and natural monkeypox virus (MPXV) infection in 100%. The initial T cell response assay took place at a median of approximately 100 days post-vaccination and 300 days post-infection. Methods: This study investigates the durability of T cell immunity in PLWH by retesting patients approximately two years after initial assessment. We were able to retest 27 of 33 vaccinated patients and 7 of 10 patients after MPXV infection. T cells were stimulated with the same orthopoxvirus-derived peptide pools as in the initial study, and interferon (IFN)-γ and interleukin (IL)-2 ELISpot assays were performed. Results: The ELISpot assays showed specific T cell responses in 59% and 86% of twice vaccinated and previously infected patients, respectively. Paired analysis revealed no significant differences between previous and current data (short- and long-term follow-up), with IL-2 ELISpot results showing positive correlations at both time points ( r = 0.67, p = 0.0001). Long-term IFN-γ responses after MPXV infection were 4.3 times higher ( p < 0.01), and IL-2 responses were 2.9 times higher ( p = 0.05) than after vaccination. Conclusions: Our data indicates that T cell responses to Orthopoxviruses remain overall stable for 2–3 years in PLWH, with long-term immunity being stronger after natural MPXV infection than after two vaccinations.