MVA-85A, a novel candidate booster vaccine for the prevention of tuberculosis in children and adults

Abstract

MVA-85A, in development by Oxford-Emergent Tuberculosis Consortium Ltd and the EU-funded research program TB-VAC, is a live attenuated viral vaccine expressing the immunodominant tuberculosis (TB) antigen 85A, and is intended for use in a heterologous prime-boost strategy to prevent TB. MVA-85A is highly immunogenic in both animals and humans, eliciting strong polyfunctional CD4+ T-cell responses when administered as a boost following BCG vaccination or when administered to individuals previously exposed to TB. Animal studies have demonstrated trends toward reduced pathology and bacillary burden for animals vaccinated with BCG prime followed by MVA-85A boost compared with BCG alone; however, these positive effects appear to be modest, and interpretation is limited by the small number of animals tested. The vaccine has an excellent safety profile in BCG-naïve, previously BCG-vaccinated and TB-exposed adults, as well as in BCG-vaccinated adolescents and children. At the time of publication, MVA-85A was in a more advanced stage of clinical development than other novel TB vaccine candidates, with a large-scale, proof-of-concept phase IIb clinical trial underway for the determination of safety, immunogenicity and prevention of TB in infants.