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Vaccine provides 54% protection against active TB in phase 2b trial
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A vaccine candidate provided 54% protection against active tuberculosis disease in adults with Mycobacterium tuberculosis infection, according to results from a phase 2b trial published in The New England Journal of Medicine.
“There were an estimated 10.4 million new cases of tuberculosis and 1.7 million deaths from the disease in 2016,” Olivier Van Der Meeren, MD, director and senior clinical research and development lead for HIV and TB vaccine development at GlaxoSmithKline, and colleagues wrote. “An effective tuberculosis vaccine for M. tuberculosis-infected persons could have a marked effect on tuberculosis control, including drug-resistant tuberculosis, through interruption of transmission.”
Van Der Meeren and colleagues conducted a phase 2b study in Kenya, South Africa and Zambia of M72/AS01E (GlaxoSmithKline), a vaccine candidate containing the M72 recombinant fusion protein derived from two immunogenic M. tuberculosis antigens combined with the ASO1 adjuvant system. They randomly assigned HIV-negative adults aged 18 to 50 years with latent M. tuberculosis infection two doses of either M72/AS01E or placebo, given intramuscularly 1 month apart.
Van Der Meeren and colleagues noted that most study participants had previously received the bacille Calmette-Guérin (BCG) vaccine, which is used to prevent childhood TB meningitis and military disease in many countries with a high prevalence of TB but is not generally recommended for use in the United States, according to the CDC.
The study measured the safety of M72/AS01E and its efficacy against the progression to bacteriologically confirmed active pulmonary TB, Van Der Meeren and colleagues said.
The newly published findings include primary analysis results of the ongoing trial after a mean of 2.3 years of follow-up. In all, 1,786 study participants received M72/AS01E and 1,787 received placebo. Participants had a mean age of 28.9 years and 43% women. The according-to-protocol efficacy cohort included 1,623 participants receiving M72/AS01E and 1,660 in the placebo arm.
According to Van Der Meeren and colleagues, 10 participants in the M72/AS01E arm and 22 in the placebo cohort developed bacteriologically confirmed active pulmonary TB, for incidence rates of .3 and .6 per 100 person-years, respectively, and an overall vaccine efficacy of 54% (95% CI, 2.9-78.2). Results were similar for the total vaccinated efficacy cohort, with a vaccine efficacy of 57% (95% CI, 9.7-79.5%).
A greater percentage of participants receiving M72/AS01E reported adverse events compared with the placebo cohort (67.4% vs. 45.4%) within 30 days after injection, Van Der Meeren and colleagues reported. 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 tuberculosis was significantly lower with M72/AS01E than with placebo among healthy M. tuberculosis-infected, largely BCG-vaccinated, HIV-negative adults,” the researchers concluded. “These promising results provide an opportunity to better understand the mechanisms by which this vaccine may confer protection against tuberculosis and support its further evaluation.”
In a related editorial, Barry R. Bloom, PhD, the Joan L. and Julius H. Jacobson Research Professor of Public Health at the Harvard T.H. Chan School of Public Health, said there has been controversy over the value of the BCG vaccine and that other trials of new TB vaccines have been disappointing. According to Bloom, “there has been here has been widespread skepticism in the scientific community that an effective tuberculosis vaccine would be technically feasible and in industry that it can be economically viable.”
Bloom noted that further research is needed before M72/AS01E could become a licensed product but said the current study “represents an important step forward toward developing an effective immunization against tuberculosis; 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 effective new vaccines can be developed for tuberculosis,” he wrote. – by Bruce Thiel
Disclosures: Bloom reports serving as an editor for the Proceedings of the National Academy of Sciences of the United States of America for a manuscript that reported the effectiveness of M72/AS01E in nonhuman primates and serving as an external reviewer of the South African TB Vaccine Initiative (SATVI) in 2015, which did not include a discussion of the vaccine. Van Der Meeren reports personal fees from GlaxoSmithKline outside the submitted work. Please see the full study for the other authors’ relevant financial disclosures.
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