Year-long assessment of the immune response elicited by MVA-BN vaccine

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-γ 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 μL. 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-γ 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.