Breakthrough infections after post-exposure vaccination against Monkeypox

BackgroundA third-generation smallpox vaccine was recommended in France for individuals who had a high-risk contact with a PCR-confirmed Monkeypox patient. We aimed to describe the outcomes of high-risk contacts receiving third-generation smallpox vaccine as an early post-exposure ring vaccination (EPRV) especially tolerance and potential breakthrough infections after the first dose. MethodsWe performed an observational analysis of all consecutive individuals vaccinated with the IMVANEX(R) smallpox vaccine after a high-risk contact defined as close skin-to-skin or mucosal contact and/or indirect contact on textile or surface and/or droplets exposure defined by a contact at less than 2 meters during at least 3 hours with a PCR-confirmed Monkeypox patient. ResultsBetween May 27th and July 13th, 2022, 276 individuals received one dose of IMVANEX(R) with a median delay of 11 days [IQR 8-14] after exposure with a confirmed Monkeypox patient. Mode of exposure was droplets for 240 patients (91%), indirect contact for 189 (71%) and unprotected sexual intercourse for 146 (54%). Most of the patients were men (91%, n=250) and men who have sex with men (88%, n=233). The vaccine was well tolerated with no severe adverse event. Among the 276 vaccinated individuals, 12 (4%) had a confirmed Monkeypox breakthrough infection with no severe infection. Ten out of 12 patients developed a Monkeypox infection in the five days following vaccination and two had a breakthrough infection at 22 and 25 days. ConclusionEPRV with a third-generation smallpox vaccine was well tolerated and effective against Monkeypox but did not completely prevent breakthrough infections.