san francisco – A new The vaccine showed efficacy in young adults – an important finding because models suggest that inducing immunity in adolescents and young adults would be the fastest and most cost-effective approach to dealing with the global TB epidemic.
CDC/Janice Carr
The study recruited adults who had previously been exposed to Mycobacterium tuberculosis, a population that receives no benefit from the long-standing bacillus Calmette-Guérin (BCG) vaccine. The overall efficacy of protection was 54%. “There isn’t any vaccine that’s been demonstrated to work in people who are already infected. It’s also the first vaccine to show this level of statistically significant protection in adults, and it’s adults who are the major transmitters of tuberculosis. The modeling has shown that even a vaccine that could protect infected adults at 20% vaccine efficacy would have a substantial impact on the epidemic and be cost effective,” said Ann Ginsberg, MD, PhD, chief medical officer at Aeras, which developed the vaccine and is now testing it in partnership with GlaxoSmithKline.
The results of the study were presented at ID Week 2018 and published in the New England Journal of Medicine (2018 Sep 25. doi: 10.1056/NEJMoa1803484).
The results address a major weakness of the BCG vaccine, which is that some studies have shown it offers little benefit to subjects who are already infected with the disease, which is the case for about a quarter of the world’s population, according to Dr. Ginsberg. The probable explanation is that previous infection with M. tuberculosis or a related bacteria is common in some populations and that this exposure grants some protection against progression to active disease.
The researchers tested the M72/AS01E vaccine, which includes two M. tuberculosis antigens that were identified from patients who had controlled their infection and also the AS01 adjuvant, which contains two immunostimulating agents and is a component of a developmental malaria vaccine and the recombinant zoster vaccine Shingrix.
In Kenya, South Africa, and Zambia, the researchers randomized 3,330 participants (mean age, 28.9 years; 43% female) to receive two doses 1 month apart of either vaccine or placebo. After a mean follow-up of 2.3 years, the protocol efficacy analysis showed that the vaccine had an efficacy rate of 54.0% (P = .04) for pulmonary tuberculosis.
The vaccine had greater efficacy in men (75.2%; P = .03) than it did in women (27.4%; P = .52) and among individuals aged 25 years or younger (84.4%; P = .01) than it did among older subjects (10.2%, P = .82).
The frequency of serious adverse events was similar between the vaccine (1.6%) and the placebo group (1.8%). Unsolicited reports of adverse events were more common in the vaccine group than the placebo group (67.4% vs. 45.4%, respectively), driven largely by more reports of injection site reactions and flu-like symptoms. Solicited reports of adverse events were highlighted by a greater frequency of injection site pain in the vaccine group (81.8% vs. 34.4%). A total of 24.3% of the vaccine recipients reported grade 3 pain, compared with 3.3% in the placebo arm. Rates of fatigue, headache, malaise, or myalgia were also higher in the vaccine group, as was fever.
All of the subjects in the vaccine group had seroconversion at month 2, and 99% remained seroconverted at 12 months.
Next, the researchers plan to conduct studies in HIV-infected individuals and to proceed with phase III trials.
The trial was funded by GlaxoSmithKline Biologicals and Aeras. Dr. Ginsberg is an employee of Aeras.
SOURCE: Ginsberg A et al. IDWeek 2018, Abstract 120