Recent Developments in Tuberculosis Vaccines

Dessislava Marinova; Jesus Gonzalo-Asensio; Nacho Aguilo; Carlos Martin


Expert Rev Vaccines. 2013;12(12):1431-1448. 

In This Article

Lessons to Be Learned From the First Efficacy Clinical Trial of MVA85A

Although the Phase IIb efficacy results with MVA85A in BCG-immunized infants were not as anticipated based on rigorous preclinical animal data,[122,145,146] the trial represents a great milestone for clinical research in South Africa and for the global TB vaccine development community providing valuable information that can serve in the future development of vaccine candidates.[92,147] The SATVI team showed top of the line team expertise through this elegantly designed, organized and conducted in the most efficient manner possible trial showing the world that conducting high-quality research at the heart of the TB epidemic in a resource limited setting is possible.[148] In this trial, approximately 3% (39 of 1395) of the infants in the BCG control group satisfied the primary definition of active TB, with conversion in 12% of the infants in this group. The poor efficacy data in the BCG control group correlated with lack of antigen-specific Th1 and Th17 CD4+ T-cell responses. Th1 and Th17 antigen-specific T-cell responses were only modestly induced following vaccination with MVA85A and correlated with lack of improvement of protection in BCG-vaccinated infants. An earlier clinical trial in Gambian infants showed reduced immunogenicity of MVA85A when administered with EPI vaccines.[87] Another clinical trial in South African infants also investigated the role of age on MVA85A immunity showing that infants and children had lower pre-vaccination Ag85A-specific T-cell responses as compared with adolescents and adults.[90] However, significantly greater responsiveness in children and infants were observed at long term after MVA85A administration. These data suggest that progress will require frank appraisal of the gaps in our understanding of protective immunity and appropriate use and interpretation of the available animal models.[124,149]