Background Modified-Vaccinia-Ankara Bavarian Nordic (MVA-BN) vaccine has been recommended to tackle the mpox epidemic 2022-2023 and its resurgence in 2024. Although its effectiveness has been estimated to range between 36-86%, the persistence of protection is still unknown. Aims of this study is to assess the immune response one year after vaccination with MVA-BN. Methods Observational prospective study at the National Institute for Infectious Diseases in Rome. All people at high risk for mpox infection who received MVA-BN as pre-exposure prophylaxis were enrolled. People previously primed with smallpox vaccination received a single-dose course of MVA-BN, while non-primed received a two-dose course. Blood samples were collected at the time of each dose and one, six and 12 months after vaccination. MPXV-specific IgG and neutralizing antibody (nAb) titers were assessed by immunofluorescence and plaque neutralization tests, respectively. Interferon-gamma producing T-cell specific response to the MVA-BN vaccine was analyzed by ELISpot assay. Antibody titers at pre- and post-vaccination were compared using the Friedman tests. Mann Whitney test was used to compare antibody titers in PLWH vs PLWoH. Wilcoxon and Mann-Whitney non-parametric tests were used to compare T-cells specific response to the MVA-BN vaccine for intra and inter-group differences, respectively. Results Fifty high-risk people were included. All were men, with 94% self-reporting having sex with men. The median age was 50 years (IQR 45-57), and 21 (42%) were people living with HIV (PLWH), all on antiretroviral therapy, and 71% with a CD4 cell count higher than 500 mmc. 25 (50%) have been primed with previous smallpox vaccination. In non-primed people, anti-MPXV IgG titers significantly increased from T1 to T3 and, despite a slight reduction, were still higher than T1 up to T4 and then gradually decreased until T5, when 64% of sera were still reactive. MPXV-nAb titers peaked at T3 and then dropped, with 56% and 32% of sera reactive at T4 and T5, respectively. IFN-g; production by MVA-BN-specific T-cells progressively rose across time, peaked at T3, and remained significantly higher than the baseline after 6 and 12 months from vaccination. A single-dose course of MVA-BN vaccination in smallpox-primed participants elicited an early increase in IgG and nAb titers, which remained significantly higher than baseline after 6 and 12 months. MPXV-nAbs were detected in 80% and 72% of vaccinees at T4 and T5, respectively. A similar improvement and maintenance were observed for the MVA-BN-specific T-cell response. No evidence for a difference in both humoral and cellular responses was found between PLWH and PLWoH in our cohort. Conclusions One year after vaccination, our data showed the persistent detectability of low levels of nAb against MPXV in one-third of non-primed individuals. At the same time, humoral response was still detectable in most previously vaccinated participants. Concurrently, the MVA-BN-specific T-cell response was robust and persistent.

AA declared Payment or honoraria for lectures/presentation by Bavarian Nordic

The study was funded by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS Advanced grant 5x1000 2021 and by the Italian Ministry of Health Ricerca Corrente Linea 2 INMI Spallanzani IRCCS.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Mpox-Vac study Studio prospettico osservazionale per monitorare aspetti relativi alla sicurezza alla efficacia alla immunogenicita e alla accettabilita della vaccinazione anti Monkeypox con vaccino MVA-BN (JYNNEOS) in persone ad alto rischio was approved by the INMI Lazzaro Spallanzani Ethical Committee (approval number 41z Register of Non-Covid Trials 2022)

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All data produced in the present study are available upon reasonable request to the authors