The vaccine provides 54% protection against active TB in the Phase 2b trial

One vaccine candidate provided 54% protection against active TB in adults with Mycobacterium tuberculosis infection, according to the results of a phase 2b trial published today in The New England Journal of Medicine.

"In 2016, an estimated 10.4 million new TB cases and 1.7 million deaths from the disease" Olivier Van Der Meeren, MD, Director and Head of Clinical Research and Head of HIV and TB Vaccine Development at GlaxoSmithKline, and their colleagues wrote. "An effective vaccine against tuberculosis for M. tuberculosisInfected persons could have a marked effect on TB control, including drug-resistant TB, by interrupting transmission. "

Van Der Meeren and colleagues conducted a phase 2b study in Kenya, South Africa and Zambia of M72 / AS01._E (GlaxoSmithKline), a vaccine candidate containing the M72 recombinant fusion protein derived from two immunogens M. tuberculosis antigens combined with ASO1 adjuvant system. They randomly assigned seronegative adults aged 18 to 50 with M. tuberculosis infection two doses of M72 / AS01_E or placebo administered intramuscularly at 1 month interval.

Van Der Meeren and colleagues noted that most of the study participants had previously received the Bacillus Calmette-Guerin (BCG) vaccine, used to prevent meningitis and military disease in children in many high-burden countries. prevalence of tuberculosis. in the United States, according to the CDC.

The study measured the safety of M72 / AS01_E and its effectiveness against the progression of bacteriologically confirmed active pulmonary tuberculosis, said Van Der Meeren and his colleagues.

The newly published results include the results of the primary analysis of the ongoing trial after an average of 2.3 years of follow-up. A total of 1,786 study participants received M72 / AS01_E and 1,787 received placebo. Participants averaged 28.9 years and 43% women. The efficacy cohort according to the protocol included 1,623 participants receiving M72 / AS01_E and 1660 in the placebo arm.

According to Van Der Meeren and his colleagues, 10 participants in M72 / AS01_E arm and 22 in the placebo cohort developed bacteriologically confirmed active pulmonary tuberculosis, for incidence rates of 0.3 and 0.6 per 100 person-years, respectively, and an overall vaccine efficacy of 54% ( 95% CI, 2.9-78.2). The results were similar for the cohort of total vaccinated efficacy, with a vaccine efficacy of 57% (95% CI, 9.7-79.5%).

A greater percentage of participants receiving M72 / AS01_E Van Der Meeren and colleagues reported adverse events compared to the placebo cohort (67.4% vs. 45.4%) within 30 days of injection. The incidence of serious adverse events, including potential immune-mediated diseases and deaths, was similar between the two treatment arms, they said.

"We found that the incidence of pulmonary TB was significantly lower with M72 / AS01_E than with placebo in healthy people M. tuberculosis-infected, largely vaccinated with BCG, seronegative adults, "concluded the researchers. "These promising results provide insights into the mechanisms by which this vaccine can provide protection against TB and support its subsequent evaluation."

In a related editorial, Barry R. Bloom, PhD, Prof. Joan L. and Julius H. Jacobson of Public Health Research at Harvard T.H. Chan School of Public Health said the value of the BCG vaccine was controversial and that other trials of new TB vaccines were disappointing. According to Bloom, "there has been widespread skepticism in the scientific community that an effective TB vaccine would be technically feasible and in industry it could be economically viable."

Bloom noted that further research is needed before M72 / AS01_E could become a registered product, but said the present study "represents an important step towards the development of effective TB vaccination; it is probably not the final iteration.

"The results reinforce the importance of international collaborations, set the stage for testing additional candidates, and offer renewed hope that new, effective vaccines can be developed for TB," he wrote. – by Bruce Thiel

Disclosures: Bloom says serving as an editor for the Proceedings of the National Academy of Sciences of the United States of America for a manuscript that reports the effectiveness of M72 / AS01_E in nonhuman primates and as an external reviewer of the South Africa Tuberculosis Vaccination Initiative (SATVI) in 2015, which did not include a discussion of the vaccine. Van Der Meeren reports GlaxoSmithKline's personal expenses outside the submitted work. Please see the full review of relevant financial information of other authors.