Phase III efficacy trial of modified vaccinia Ankara as a vaccine against smallpox

Adverse events associated with traditional smallpox vaccines—which are based on replicating vaccinia viruses—underscore the need for safer alternatives, given that many countries are stockpiling vaccine in case of a reemergence.

Adverse events associated with traditional smallpox vaccines—which are based on replicating vaccinia viruses—underscore the need for safer alternatives, given that many countries are stockpiling vaccine in case of a reemergence. One prospect under development is modified vaccinia Ankara (MVA), which researchers evaluated in a Phase III efficacy trial. According to randomized assignment, 208 participants received two doses of MVA followed by a single dose of ACAM2000, an established replicating-vaccinia vaccine. An additional 213 participants received one dose of ACAM2000 alone. Measured at peak, investigators documented a geometric mean titer of neutralizing antibodies of 153.5 at week 6 for the MVA group vs. 79.3 at week 4 for the ACAM2000 group. The second co-primary outcome was attenuation of the major cutaneous reaction associated with ACAM2000. The results indicated the MVA vaccination ahead of ACAM2000 limited lesion areas to a mean 0 mm2 in the MVA recipients, achieving an attenuation ratio of 97.9%. The ACAM2000-only patients, meanwhile, presented median lesion areas measuring 76.0 mm2 and suffered more adverse events than their MVA counterparts. The findings suggest that MVA is a safe and effective vaccine against variola infection.