Study authors recommend further investigation of M72/AS01E for tuberculosis prevention and consider the trial results progress toward an efficacious vaccine.
Prevention is a key component in the effort to reach the World Health Organization’s (WHO) goal of ending tuberculosis (TB) by 2030. WHO recommendations call for a TB vaccine with at least 50% efficacy over the course of at least 2 years. A previous analysis of a trial of the M72/AS01E vaccine candidate showed 54% protection for adults with Mycobacterium tuberculosis infection who did not show evidence of active tuberculosis disease.
In a new study, investigators set out to assess the efficacy of M72/AS01E in preventing active pulmonary tuberculosis disease, according to the first case definition, bacteriologically confirmed pulmonary tuberculosis not associated with HIV.
The results of the 3-year final analysis of efficacy, safety, and immunogenicity have now been published in The New England Journal of Medicine. Results indicate that M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years, with a vaccine efficacy at 36 months of 49.7%.
Between August 2014 and November 2015, investigators enrolled adults aged 18 to 50 years with M tuberculosis infection who did not test positive for HIV at centers in South Africa, Kenya, and Zambia. Individuals were randomly assigned in a 1:1 ratio to receive 2 doses of M72/AS01E or placebo, 1 month apart. Participants were followed for 3 years after receiving the vaccine, with safety assessed in all participants who received at least 1 dose of the candidate vaccine or placebo. Participants with confirmed tuberculosis were retested for HIV, and all participants were retested for HIV at their final trial visit.
Of the 3575 participants who underwent randomization, 3573 received at least 1 dose and 3330 participants received both planned doses. Of the 3289 individuals in the according-to-protocol efficacy cohort, 13 of 1626 participants in the M72/AS01E had cases of tuberculosis that met the first case definition, compared to 26 of 1663 participants in the placebo group.
This indicated a vaccine efficacy at month 36 of 49.7%. Among participants in the vaccine group, the concentrations of M72-specific antibodies and frequency of M72-specific CD4+ T cells increased after the first dose and persisted through the follow-up period. Deaths, serious adverse events, and potential immune-mediated diseases occurred with similar frequency between the vaccine and placebo groups.
Investigators considered 2 serious adverse events to be related to the trial regimen. One adverse event was a case of pyrexia in the M72/AS01E group with onset occurring on the day of the second dose. The other trial-related adverse event was a case of hypertensive encephalopathy in the placebo group on the day of the first dose. Of the 47 deaths occurring in the study population during the trial period, none were determined by investigators to be related to the trial regimen.
Study authors recommended larger and longer studies, conducted in a broader range of populations, to confirm their results. The results support further investigation of M72/AS01E as a means of tuberculosis control and indicates progress toward a vaccine which meets the WHO’s recommendations.