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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approved by the Local ethic committee named HUPNVS Ethics Committee. This committee is made up of professionals (caregivers, doctors and administrators) from the hospital Bichat-Claude Bernard and Paris Cite University, user representatives and philosophers. website : I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors