(A-361) Vaccinia vaccine effectiveness against mpox virus infections: a living literature review and evidence synthesis

Background: Mpox, originally a zoonotic disease endemic to Central and West Africa, has recently caused global outbreaks of Clade IIb (since 2022) and Clade Ib (ongoing since 2024 in the Democratic Republic of Congo). Case expansion to historically non-endemic areas, including the US and Europe, led WHO to declare a public health emergency of international concern. Vaccinia vector-based vaccines, developed for protection against smallpox, provide some cross protection against Mpox and recently deployed to endemic areas. However, significant gaps remain in understanding vaccine effectiveness across populations and epidemiological settings.

Objectives: To conduct a living (ongoing), comprehensive literature review to summarize Vaccinia vaccine effectiveness against Mpox infections and identify residual critical gaps.

Methods: Utilizing principles of rapid living reviews, we conducted an initial literature search in October 2024 and subsequent monthly updates. Relevant terms were identified and searched for in PubMed and Embase (Ovid). Studies of mpox infections as the primary outcome and reporting either vaccine effectiveness or a measure of association between vaccination and mpox disease are reviewed. Study characteristics and reported estimates are described.

Results: As of January 2nd, 2025, eighteen unique relevant articles were identified from a total of 4,618 records. Effectiveness estimates for the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine administered as pre-exposure (PrEP, 14 studies) or post-exposure (PEP, 2 studies) prophylaxis were reported from studies conducted in North America, Europe, and Israel during or after the 2022 global outbreak. Most studies involved at-risk MSM or predominantly male populations aged ≥18 years. Effectiveness estimates of a single dose of MVA-BN administered as PrEP (14 studies) ranged from 23 to 93% (median 73%, interquartile range (IQR): 58-84%) while estimates for two doses (8 studies), ranged from 57 to 90% (median 79%, IQR: 63-86%). Effectiveness increased with time since vaccination (limited to up to >14 days) across studies reporting time-stratified data, with up to 68 to 79%. In two studies of MVA-BN administered as PEP, effectiveness estimates were -4% and 84%.

Conclusions: Despite variability in study methodology, MVA-BN is effective against mpox, but additional data is needed in immunocompromised, gender diverse, low- and middle-income countries and maternal/pediatric populations. As mpox epidemiology evolves, ongoing living systematic assessments of new evidence are needed to detect and address gaps in global vaccination strategies.