Efficacy and Safety of the Smallpox Vaccine for Postexposure Prophylaxis in Monkeypox: Protocol for an Open-Labeled, Single-Armed Study

BACKGROUND: In May 2022, a case of monkeypox (currently known as “mpox”) with no history of overseas travel was reported in the United Kingdom, followed by reports of infections reported in Europe, the United States, and other countries worldwide. Due to the significant overlap in immune responses among viruses of the genus Orthopoxvirus (including smallpox virus, mpox virus, and vaccinia virus), it is believed that cross-immunity can be achieved by administering the smallpox virus vaccine. In Japan, a smallpox vaccine (LC16m8 strain vaccine) has been approved; however, there was no regulatory approval for the mpox vaccine during the design of this study. Although it is believed that individuals exposed to the mpox virus may receive smallpox vaccination as mpox prophylaxis, the existing evidence is not clear. OBJECTIVE: The primary objective was to evaluate the efficacy of the LC16m8 strain vaccine, approved for smallpox in Japan, for postexposure prophylaxis against mpox when administered to close contacts of individuals with mpox. The secondary objective was to investigate the safety of the vaccine for postexposure prophylaxis against mpox. METHODS: The study aimed to enroll 100 vaccinated participants who had been identified as close contacts of individuals with mpox. Consent was obtained, and the participants are inoculated with the vaccine. Daily recordings of symptoms (body temperature, headache, rash, and side effects) were made until day 21 and then again on day 28. Furthermore, additional evaluations of adverse events were performed by the investigators on days 7, 14, 21, and 28. Considering that the maximum incubation period for mpox is 21 days, the primary end point is the presence or absence of the disease 21 days after close contact. The primary analysis focused on cases within 4 days of intense contact as it has been reported that vaccination within this timeframe can reduce the incidence of the disease. RESULTS: The first trial participant was enrolled on July 28, 2022, and the research period concluded in March 2023. The study results will be published in a peer-reviewed scientific journal. CONCLUSIONS: This study allowed us to investigate the efficacy and safety of the LC16m8 strain vaccine in postexposure prophylaxis against mpox. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031220137; https://jrct.niph.go.jp/en-latest-detail/jRCTs031220137 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46955