A phase 4, open-label, single arm, multi-center study to evaluate the safety of a smallpox vaccine in previously vaccinated individuals

ACAM2000® [Smallpox and Mpox (Vaccinia) Vaccine, Live] is an attenuated vaccinia vaccine indicated in the US for active immunization for the prevention of smallpox and mpox disease in individuals determined to be at high risk for smallpox or mpox infection. The current study assessed the ability of a screening algorithm to identify a population of previously vaccinated individuals for whom revaccination with ACAM2000 vaccine could be used to assess safety (NCT02443623). Vaccination in this study stimulated anti-vaccinia antibodies in plasma donors for the preparation of vaccinia immune globulin intravenous (VIGIV). This was an open label, single-arm, multi-center study. The protocol criteria were designed to screen out individuals with risk factors associated with increased risk of adverse events, specifically myocarditis/pericarditis, including an algorithm to be followed in the event of symptom development. Post-vaccination safety data was collected including solicitation for symptoms of myocarditis/pericarditis. There were 4088 participants screened, of which 3032 were vaccinated, 850 failed the screening criteria and 206 were enrolled but not vaccinated. The median age was 51, ranged from 18 to 65, and was comprised of 75% males. Out of the 3032 vaccinated participants, 1420 (47%) reported 2478 adverse events (AEs), of which 1468 AEs in 1190 (39.2%) participants were considered related. Twenty-one participants (0.7%) reported severe events, serious adverse events were uncommon (0.8%), two were considered related to vaccination and there was one unrelated death. Inadvertent autoinoculation was reported in six participants but did not require medical intervention. The most frequently reported vaccination related AEs were cutaneous reactions and constitutional symptoms. Out of 3032 vaccinated participants, 65 had potential symptoms of myocarditis/pericarditis (myopericarditis) which were resolved, and there were no diagnoses of myopericarditis. Administration of ACAM2000 vaccine was well tolerated in this population of previously vaccinated participants.