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. 2015 Apr 16;10(4):e0122653.
doi: 10.1371/journal.pone.0122653. eCollection 2015.

Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population

Eva-Maria Zitzmann-Roth  1 , Frank von Sonnenburg  2 , Stephan de la Motte  3 , Nathaly Arndtz-Wiedemann  4 , Alfred von Krempelhuber  4 , Nadine Uebler  4 , Jens Vollmar  4 , Garth Virgin  4 , Paul Chaplin  4
Affiliations

Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population

Eva-Maria Zitzmann-Roth et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: SM received honoraria as clinical investigator in this trial. NA and PC are employed for and hold stocks/warrants in Bavarian Nordic. AK, NU, JV and GV were employed by Bavarian Nordic at the time of conduct of the trial. EZ is working as cardiologist in her own private practice, called in German 'Praxis Zitzmann-Roth'. This is no employment, but a private physician practice. SM was employed by Harrison Clinical Research GmbH at the time of this trial. He is still employed with this company, that was in the meantime renamed to SyteractHCR. Harrison Clinical Research GmbH was contracted by Bavarian Nordic as a clinical service provider for this trial. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. 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.
MVA: Modified Vaccinia Ankara; FAS: full analysis set: PP: per protocol
See this image and copyright information in PMC

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