This is an enhanced safety surveillance Phase 4 study that will occur within the military Service Member population.

Primary Objective: To evaluate the rates of suspected, probable, and confirmed myocarditis and/or pericarditis in temporal association with ACAM2000® vaccination.

Secondary Objectives: To evaluate the rates of cardiovascular adverse events in temporal association with ACAM2000® vaccination.

To evaluate the rates of neurological adverse events in temporal association with ACAM2000® vaccination.

Results

On September 15, 2021, Vaccine published the results of this clinical trial.

897,227 military service members (SM) who received ACAM2000 smallpox vaccine and 450,000 SM who received Dryvax smallpox vaccine were included in the surveillance population. The rate of adjudicated myopericarditis among ACAM2000 smallpox vaccine recipients was 20.06/100,000 and was significantly higher for males (21.8/100,000) than females (8.5/100,000) and for those < 40 years of age (21.1/100,000) than for those 40 years or older (6.3/100,000). Overall rates for any cardiovascular event (Group 1 plus Group 2) were 113.5/100,000 for ACAM2000 vaccine and 439.3/100,000 for Dryvax vaccine; rate ratio, 0.26 (95% CI, 0.24-0.28). The rates of subjects with one or more defined neurological events were 2.12/100,000 and 1.11/100,000 for ACAM2000 and Dryvax vaccines respectively; rate ratio, 1.91 (95% CI, 0.71-5.10).

Conclusions: Electronic records surveillance of the entire vaccinated SM population over a ten-year period found rates of myopericarditis, of defined neurological events, and of overall cardiac events that were consistent with those of prior passive surveillance studies involving Dryvax or ACAM2000 smallpox vaccines.