BACKGROUND: Conventional smallpox vaccines based on replicating vaccinia virus 
(VV) strains (e.g. Lister Elstree, NYCBOH) are associated with a high incidence 
of myo-/pericarditis, a severe inflammatory cardiac complication. A new smallpox 
vaccine candidate based on a non-replicating Modified Vaccinia Ankara (MVA) 
poxvirus has been assessed for cardiac safety in a large placebo-controlled 
clinical trial.
METHODS: Cardiac safety of one and two doses of MVA compared to placebo was 
assessed in 745 healthy subjects. Vaccinia-naïve subjects received either one 
dose of MVA and one dose of placebo, two doses of MVA, or two doses of placebo 
by subcutaneous injection four weeks apart; vaccinia-experienced subjects 
received a single dose of MVA. Solicited and unsolicited adverse events (AE) and 
cardiac safety parameters (recorded as Adverse Events of Special Interest, AESI) 
were monitored after each injection.
RESULTS: A total of 5 possibly related AESI (3 cases of palpitations, 2 of 
tachycardia) were reported during the study. No case of myo- or pericarditis 
occurred. One possibly related serious AE (SAE) was reported during the 6-month 
follow-up period (sarcoidosis). The most frequently observed AEs were injection 
site reactions.
CONCLUSIONS: Vaccination with MVA was safe and well tolerated and did not 
increase the risk for development of myo-/pericarditis.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00316524.