Effectiveness of one dose of MVA-BN smallpox vaccine against monkeypox in England using the case-coverage method
Authors: Bertran Marta , Andrews Nick , Davison Chloe , Dugbazah Bennet , Boateng Jacob , Lunt Rachel , Hardstaff Jo , Green Melanie , Blomquist Paula , Turner Charlie , Mohammed Hamish , Cordery Rebecca , Mandal Sema , Campbell Colin , Ladhani Shamez N , Ramsay Mary , Amirthalingam Gayatri , Bernal Jamie Lopez 
Published: December 2022

AbstractBackgroundLike many other countries worldwide, the UK experienced a national outbreak of monkeypox disease in May 2022, with case numbers rising rapidly, mainly among gay, bisexual and other men who have sex with men (GBMSM). To control the outbreak, Modified Vaccinia Ankara–Bavaria Nordic (MVA-BN), an attenuated smallpox vaccine, was offered to high-risk GBMSM. We assessed the effectiveness of a single MVA-BN dose against monkeypox disease in high-risk GBMSM.MethodsMonkeypox cases in England were sent questionnaires collecting information on demographics, vaccination history and symptoms. Returned questionnaires with a rash onset date (or alternative proxy) between July 04 and October 09, 2022 were included. Females, heterosexual men, and those with missing vaccination information were excluded. Vaccine effectiveness was calculated using the case-coverage method where vaccine coverage among cases is compared to coverage in the eligible population, estimated from doses given to GBMSM and the estimated size of high-risk GBMSM. Sensitivity analysis included +/-20% differences in estimated high-risk GBMSM population size.FindingsVaccine uptake among eligible GBMSM increased steadily from July 2022, reaching 47% by October 09, 2022. Of the 363 confirmed cases, 8 occurred ≥14 days after vaccination, 32 within 0-13 days after vaccination, and the rest were unvaccinated. The estimated vaccine effectiveness ≥14 days after a single dose was 78% (95% CI: 54%-89%), with a range of ±7% in sensitivity analyses. Vaccine effectiveness within 0–13-days after vaccination was -4% (95% CI: -50% to 29%).InterpretationA single MVA-BN dose was highly protective against monkeypox disease among high-risk GBMSM.FundingNoneResearch in contextEvidence before this studyWe searched PubMed using the terms ‘monkeypox’, ‘MVA’ and ‘vaccine’, with no time limit, and used the snowball process to identify additional relevant publications. We also searched websites of regulatory authorities (FDA, EMA) for any data used during the regulatory approval processes. We also scoped pre-print databases vaccine effectiveness studies during the current outbreak. Only publications related to the Modified Vaccinia Ankara – Bavaria Nordic (MVA-BN) vaccine were included. In the UK, MVA-BN was offered to high-risk GBMSM to control a national outbreak which began in May 2022. MVA-BN is now licensed against smallpox in the US, Europe and the UK, there are, however, limited data on vaccine effectiveness against monkeypox. Preclinical studies indicated two vaccine doses were immunogenic and generated antibody levels considered protective against smallpox. Vaccine-induced antibodies are also cross-protective against monkeypox virus in vitro and in animal models. A recent, as yet unpublished, Israeli study estimated 79% vaccine effectiveness after one dose in high-risk GBMSM, while a US study reported unvaccinated individuals to be 14 times more likely to develop monkeypox disease than vaccinated persons.Added value of this studyFew countries have recommended or introduced large-scale vaccination against the current global outbreak of monkeypox disease among GBMSM in non-endemic countries. The offer of MVA-BN to high-risk GBMSM through sexual health clinics in England provided a unique opportunity to rapidly assess vaccine effectiveness after a single dose using the case-coverage method, which involves comparing vaccine coverage in cases to vaccine coverage in the eligible population. Our vaccine effectiveness estimate of 78% at least 14 days after one MVA-BN dose is consistent with Israeli estimates and provided additional evidence of a lack of protection during the first 13 days after vaccination.Implications of all the available evidenceA single dose of MVA-BN is highly protective against monkeypox disease and provides a useful tool for outbreak control when rapid protection may be needed. Given the lack of effectiveness in the first 13 days after the first dose and a median incubation period of 8-9 days after exposure to the virus, vaccination is likely to be most effective when offered as pre-exposure rather than prophylaxis. Because of the high vaccine effectiveness after one MVA-BN dose, in outbreaks where number of at-risk individuals exceed vaccine supply of two-doses, there may be benefit in prioritising delivery of first doses at the expense of delaying the second dose.