Previous studies have shown that the M72/AS01_E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01_E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13).

In each cohort, 18–59-year-old adults were randomised (1:1) to receive two doses of M72/AS01_E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective.

Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01_E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01_E participant). Robust and persistent M72-specific humoral and polyfunctional CD4⁺ T-cell-mediated immune responses were observed post-M72/AS01_E vaccination in each cohort. In conclusion, the M72/AS01_E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment.

ClinicalTrials.gov: NCT01424501