The M72/AS01 vaccine shows efficacy against pulmonary tuberculosis (TB) at 3 years postvaccination in participants with Mycobacterium tuberculosis, according to a study published in The New England Journal of Medicine.
TB remains the leading cause of death from a single pathogen, according to the World Health Organization (WHO). Vaccines that are safe and effective against TB are key to ending this epidemic. The WHO has stated that new TB vaccines for patients with or without M tuberculosis infection should have at least 50% efficacy against bacteriologically confirmed TB and that this efficacy should be sustained for at least 2 years and, ideally, 10 years.
The candidate vaccine M72/AS01 contains a recombinant fusion protein derived from 2 M tuberculosis antigens and is combined with the AS01 adjuvant system. A previous analysis of this trial (ClinicalTrials.gov identifier: NCT01755598) suggested that this vaccine provided 54.0% protection against active pulmonary TB disease and had no safety concerns. Therefore, this double-blind, randomized, placebo-controlled study provided the 3-year analysis results for the efficacy, safety, and immunogenicity of M72/AS01.
The trial followed 3575 participants from Kenya, South Africa, and Zambia who had M tuberculosis infection without evidence of active disease. M tuberculosis infection was defined by positive results on interferon-g release assay. The participants were randomly assigned to 1 of 2 groups that received 2 doses of either M72/AS01 or placebo. The doses were administered 1 month apart, and a total of 3573 participants received at least 1 dose of either M72/AS01 or placebo and 3330 participants received both doses.
The study’s primary objective was to evaluate the efficacy of M72/AS01 in preventing active pulmonary TB disease as per the first case definition: bacteriologically confirmed pulmonary TB that is not associated with HIV infection.
After receipt of the second dose, participants were followed for 3 years. Sputum samples for polymerase chain reaction assay and/ or mycobacterial culture were collected from participants with clinical suspicion of TB. In a subgroup of 300 participants, humoral and cell-mediated immune responses were evaluated until month 36.
Results showed that M72/AS01 vaccine efficacy against pulmonary TB and vaccine-induced immune responses were sustained for 3 years in all participants. In the efficacy cohort (n=3289), 13 (<1%) participants in the M72/AS01 group and 26 (2%) in the placebo group had TB that met the first-case definition (incidence, 0.3 vs 0.6 cases per 100 person-years, respectively). At month 36, the vaccine efficacy was 49.7% (95% CI, 2.1-74.2). Further, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T-cells increased after the first dose and were sustained throughout the follow-up period. In the placebo group, there was no significant change in polypositive M72-specific CD4+ T-cell frequencies.
The rates of serious adverse events, potential immune-mediated diseases, and deaths were similar between groups. Two serious adverse events were considered to be related to the trial regimen: a case of pyrexia in the M72/AS01 group and a case of hypertensive encephalopathy in the placebo group. Eight potential immune-mediated diseases that affected a variety of organ classes were reported: 2 in the M72/AS01 group and 6 in the placebo group. In total, there were 47 deaths during the trial: 19 (1.1%) in the M72/AS01 group and 28 (1.6%) in the placebo group (P =.24); however, the investigators determined that no deaths were related to the trial regimen. The most common cause of death was trauma.
Overall, the study authors concluded that, among adults infected with M. tuberculosis, vaccination with M72/AS01 elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years.
Disclosure: This clinical trial was supported by GlaxoSmithKline Biologicals and Aeras through the International AIDS Vaccine Initiative. Please see the original reference for a full list of authors’ disclosures.
Tait DR, Hatherill M, Van Der Meeren O, et al. Final analysis of a trial of M72/AS01 vaccine to prevent tuberculosis [published online October 29, 2019]. NEJM. doi:10.1056/NEJMoa1909953