Tuberculosis subunit vaccine shows promising results in phase IIb study

The incidence of primary tuberculosis was significantly lower after the administration of the M72 / AS01 subunit_E vaccine compared to placebo, a phase IIb trial found.

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

The vaccine was mostly safe with more side effects in the vaccine group compared to placebo, but a similar number of serious adverse events, immune-mediated diseases and deaths between groups, the authors wrote in the New England Journal of Medicine.

The study was published to coincide with the high-level meeting of the United Nations General Assembly in New York on the fight against tuberculosis.

The study is timely because, as the authors have written, "the most effective contribution to TB control would be a vaccine against pulmonary TB in adolescents and young adults".

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

In addition, the researchers found that phase II trials of M72 / AS01_E the vaccine had "a clinically acceptable safety profile and induces humoral and cell-mediated immune responses in healthy and HIV-infected individuals, M. tuberculosisInfected adults and adolescents and infants vaccinated with BCG. "

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

Participants were healthy HIV-positive adults aged 18 to 50 years who did not have any symptoms of tuberculosis, but who were QuantiFERON-Gold In-Tube (QFT) positive, with a negative sputum M. tuberculosis initially via the polymerase chain reaction test. The primary case definition was "active primary tuberculosis confirmed bacteriologically, 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 had an average age of about 29 years and 43% were women and were "largely vaccinated with BCG".

The effectiveness analysis according to the protocol counted 3,283 participants – 1,623 in the M72 / AS01._E group and 1660 in the placebo group. In total, 10 cases of active primary tuberculosis in the vaccinated group and 22 cases in the placebo group met the definition of the primary case 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 efficacy of the vaccine 54.0%).

In terms of safety, the M72 / AS01_E the vaccinated group had more reports of unsolicited adverse events (67.4%) than placebo (45.4%), although the authors noted that this was due to site reactions. injection and flu-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 the vaccinated group, 1.8% in the control group). A serious adverse event in each group (pyrexia and hypertensive encephalopathy, even if the groups were still blind) was considered to be associated with the study treatment. There were 24 deaths (seven in the M72 / AS01_E group, 17 in the placebo group), but the authors stated that no one was related to the test regimen.

Pre-specified subgroup analyzes using case definition 1 showed that the efficacy of the vaccine in men was 75.2% (P= 0.03) and in women, 27.4% (P= 0.52), while it was 84.4% (P= 0.01) in adults aged ≤ 25 and 10.2% (P= 0.82) in adults 25 years of age and older.

This was noted in an accompanying editorial by Barry Bloom, PhD, of Harvard's TH Chan School of Public Health in Boston, who argued that the overall effectiveness of the 54% vaccine establishes a proof of principle but still requires some adjustments.

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

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

2018-09-25T14: 30: 00-0400