Experimental tuberculosis vaccine shows sustained protection

Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis

T (TB) is a curable, chronic lung disease. Despite this, it remains one of the deadliest infectious diseases of this day and age. It caused an estimated 1.5 million deaths worldwide last year alone and is the . It’s estimated that one in four people worldwide carry latent TB (they are carriers but don’t get sick and can’t transmit the disease). Around 10% of them will develop active TB, and people with compromised or weakened immune systems are more vulnerable.

The vaccine we currently use against TB, the Bacille-Calmette-Guerin (BCG) vaccine, was licensed for human use way back in 1921 and has only been proven effective for limited forms of the disease in children under five. The BCG vaccine is typically given to children in countries where the prevalence of TB is high. It is rarely given to adults because it varies in effectiveness in preventing pulmonary TB.

However, a in three African nations showed the vaccine to have a 50% protection against progression to active tuberculosis disease three years after it was given to individuals infected with Mycobacterium tuberculosis but without symptoms. The study was sponsored by GlaxoSmithKline and conducted in partnership with IAVI, a non-profit organization dedicated to developing vaccines against HIV and TB.

In individuals infected, a vaccine offered some protection for at least 3 years in a placebo-controlled trial. Participants in the trial were healthy, HIV-negative adults ages 18–50 years old with latent tuberculosis infection without evidence of active tuberculosis disease. The per-protocol efficacy cohort comprised 3,289 participants. Following a mean 2.7 years of follow-up, 13 cases of active pulmonary tuberculosis developed in the vaccine group and 26 in the placebo group. In addition, there was lower incidence of tuberculosis in the vaccine group compared to the placebo group (0.3 vs 0.6 cases per 100 person-years, respectively), which was unchanged from a prior analysis of the data, the authors wrote in a special early release of the

Furthermore, increases were seen in M72-specific antibody concentration and frequencies of M72-specific CD4+ T cells after dose one in the vaccine group. Safety was also comparable between groups. The study was published to coincide with the 50th in Hyderabad, India.

In September 2018, a proof-of-principle study found that the GSK M72/AS01E vaccine against TB disease, with 54.0% vaccine efficacy. The authors noted that analysis of the primary objective of the prior trial was performed when all participants had completed at least 2 years of follow-up. This current analysis is the final efficacy and safety analyses following 3 years of follow-up. The prior analysis had found a higher percentage of vaccine efficacy for participants age 25 and younger compared to those who were older than age 25. Humoral (antibody-mediated) immune response was “consistent” with prior experiences with the vaccine, with responses sustained until month 36, the authors noted.

Examining safety, there were two serious adverse events — one fever in the vaccine group and a case of hypertensive encephalopathy in the placebo group. Overall, there were 49 deaths during the trial period — 19 in the vaccine group and 28 in the placebo group, though none were determined to be related to the vaccine.

The authors concluded that the study results still need confirmation in larger trials, over longer time periods and in more diverse populations. The latter should include people who test negative for tuberculosis via diagnostic testing, the investigators said, as well as a wider variety of ethnic backgrounds, ages and geographic locations. The vaccine will probably only be ready to use in those who need it most by 2028, reports.

South African Tuberculosis Vaccine Initiative (SATVI) Director Professor Mark Hatherill said a vaccine would be “the only way in the short-term to interrupt TB transmission and get control of the epidemic”. If successful, the vaccine could prevent millions of new TB cases and subsequent deaths all over the globe.

Physician-Scientist FRSPH FRSA • GlobalHealth | Infectious Diseases | Digital Health • Writes about innovation, vaccines, pathogens, outbreaks, public health