Abstract Body

Background

The current mpox resurgence raised the question of the residual immune protection conferred by the MVA-BN vaccination received during the 2022 outbreak. Available data on long-term immune response after MVA-BN are scarce, especially in PWH with low CD4 count, who are at high risk of severe and prolonged mpox and a possible impaired vaccine immune response. We described humoral, and T-cell immune responses elicited up to two years from MVA-BN vaccination, stratifying results according to HIV infection and CD4 count to provide elements to establish the need for a vaccine boost.

Methods

Blood samples from people receiving a primary two-dose course of MVA-BN were prospectively collected at the time of each dose administration (T1-T2) and then after 1 (T3), 6 (T4), 12 (T5) and 24 (T6) months. Neutralizing antibodies (nAbs) were assessed by a 50% plaque reduction neutralization test and interferon-γ producing MVA-BN specific T-cells by ELISpot assay. Data at T6 were stratified according to HIV infection and CD4 count (<350 and >350). Kruskal-Wallis with Dunn tests, Wilcoxon, and Mann-Whitney tests were used for statistics.  

Results

All the 40 people enrolled were MSM, not primed for smallpox during childhood, with a median age of 41.5 years (IQR 35-45). Among the 20 (50%) PWH, 9 (45%) had a CD4 count <350 mmc. After peaking one month from vaccination, nAb titers progressively dropped in the following time points, with less than 25% of sera reactive at two years (T6). 

The MVA-BN-specific T-cell response raised early after vaccination, remained stable until one year, and significantly decreased at two years (p=0.02). At that time, no evidence for a difference was detected between PWoH and PWH with CD4 count <350 or >350, both for cellular and neutralizing response.

Conclusions

Two years after receiving MVA-BN, regardless of HIV infection and CD4 count, a poor neutralizing response was detected, while T-cell response persisted despite being substantially diminished. A booster MVA-BN dose at least two years after the primary cycle seems necessary both to reactivate the humoral response and recall the residual cellular response, accounting for most of the clinical protection observed so far.