Breakthrough infections after post-exposure vaccination against Monkeypox

Background A 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. Methods We performed an observational analysis of all consecutive individuals vaccinated with the IMVANEX 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. Results Between May 27th and July 13th, 2022, 276 individuals received one dose of IMVANEX 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. Conclusion EPRV with a third-generation smallpox vaccine was well tolerated and effective against Monkeypox but did not completely prevent breakthrough infections.