Cardiac Safety of Modified Vaccinia Ankara for Vaccination against Smallpox in a Young, Healthy Study Population

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 nonreplicating 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-naive 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

Related Adverse Events with a frequency of ≥2% in at least one study group; MedDRA Coding by System Organ Class and Preferred Term (Safety dataset).

<p>Fishers Exact test of comparison to Group 3; NS = Not Significant (p≥0.05);</p><p>* p< 0.05;</p><p>** p<0.01;</p><p>*** p < 0.001).</p><p>Related Adverse Events with a frequency of ≥2% in at least one study group; MedDRA Coding by System Organ Class and Preferred Term (Safety dataset).</p

Consolidated Standards of Reporting Trials (CONSORT) subject flow diagram demonstrating the number of patients recruited into the study, number of subjects randomized and vaccinated, and number of subjects analyzed.

<p>MVA: Modified Vaccinia Ankara; FAS: full analysis set: PP: per protocol</p