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The incidence of primary tuberculosis was significantly lower following administration of the subunit M72/AS01_E vaccine compared with placebo, a phase IIb trial found.

In a randomized trial, vaccine efficacy for the M72/AS01_E tuberculosis vaccine was 54.0% (95% CI 2.9-78.2, P=0.04) versus those who received placebo, reported Olivier Van Der Meeren, MD, of GlaxoSmithKline in Belgium, and colleagues.

The vaccine was mostly safe with more adverse events in the vaccine group versus placebo, but a similar number of serious adverse events, immune-mediated diseases, and deaths between groups, the authors wrote in

The study was released to coincide with the United Nations General Assembly High-Level Meeting in New York City on the fight against tuberculosis.

The study is timely because, as the authors wrote, "the most effective contribution to tuberculosis control would be a vaccine preventing pulmonary tuberculosis in adolescents and young adults."

However, the only licensed vaccine, the BCG (bacille Calmette-Guérin) vaccine, does not offer "substantial protection" against tuberculosis in adults with Mycobacterium tuberculosis infection.

Moreover, the researchers found that phase II trials of the M72/AS01_E vaccine had "a clinically acceptable safety profile and induced humoral and cell-mediated immune responses in healthy and ... HIV-infected persons, M. tuberculosis-infected adults and adolescents and BCG-vaccinated infants."

This multicenter phase IIb proof-of-concept study examined the vaccine in preventing bacteriologically confirmed tuberculosis in HIV-negative adults with M. tuberculosis infection, as defined by a positive interferon-γ release assay.

Participants were healthy, HIV-negative adults ages 18-50 who had no symptoms of tuberculosis, but were QuantiFERON-Gold In-Tube assay (QFT)-positive, with a sputum sample that was negative for M. tuberculosis at baseline via polymerase chain reaction assay. The primary case definition was "bacteriologically confirmed active primary tuberculosis, with confirmation before treatment."

A total of 3,573 participants received at least one dose of vaccine or placebo, and 3,330 received both doses. Participants were a mean age of approximately 29, and 43% were women and were "largely BCG-vaccinated."

The according-to-protocol efficacy analysis had 3,283 participants -- 1,623 in the M72/AS01_E group and 1,660 in the placebo group. There were a total of 10 cases of active primary tuberculosis in the vaccine group and 22 in the placebo group who met the primary case definition after a follow-up period of about 2.3 years. The incidence of pulmonary tuberculosis per 100 person years was 0.3 cases in the M72/AS01_E group and 0.6 cases in the placebo group (overall vaccine efficacy of 54.0%).

In terms of safety, the M72/AS01_E vaccine group had more unsolicited reports of adverse events (67.4%) compared with placebo (45.4%), although the authors noted this was driven by injection-site reactions and influenza-like symptoms. However, there was a similar percentage of participants with at least one serious adverse event within 6 months after the last dose in both groups (1.6% in vaccine group, 1.8% in control group). One serious adverse event in each group (pyrexia and hypertensive encephalopathy, though groups were still blinded) was considered to be related to the trial regimen. There were 24 deaths (seven in the M72/AS01_E group, 17 in the placebo group), but the authors said none were related to the trial regimen.

Prespecified subgroup analyses using case definition 1 found that vaccine efficacy among men was 75.2% (P=0.03) and among women, 27.4% (P=0.52), while it was 84.4% (P=0.01) among adults age ≤25 and 10.2% (P=0.82) among adults age ≥25.

This was noted in an by Barry Bloom, PhD, of the Harvard T.H. Chan School of Public Health in Boston, who argued that the overall vaccine efficacy of 54% establishes proof of principle, but still needs some fine-tuning.

"One critical question, which can be addressed with biobanked samples from a subgroup of the trial participants, is what are the immunologic and gene-expression differences between those who were protected and those who were not," he wrote. "This has the potential to reveal correlates or biomarkers of protection that currently do not exist, which could greatly reduce the time and costs of future trials."

Van Der Meeren and colleagues characterized the results as "promising" and said they support further evaluation of the vaccine.