Glimmer of hope for vaccine that could eradicate TB reinfection

Tuberculosis reinfection may be a thing of the past if a vaccine that is being developed by the University of Cape Town researchers proves successful.

The results from a clinical trial that is investigating a candidate vaccine that prevents the recurrence of TB in people who’ve recovered from the disease shows promise after it was proved safe and induced an immune response when given to cured patients.

The results of the phase 2 trial of the ID93+GLA-SE candidate vaccine, which have been published in the Lancet, suggest that the vaccine could potentially be used as a therapeutic vaccine for prevention of post-treatment TB recurrence. Other researchers involved in the study are from Stellenbosch University, TASK Applied Science, Fred Hutchinson Cancer Research Institute and the Infectious Disease Research Institute.

Between June 2015 and May 2016 researchers assessed 177 HIV-negative people in the Western Cape who had been cured of TB. Participants were enrolled after completing standard treatment and randomly assigned to receive vaccine or placebo in three cohorts, including ID93, GLA-SE and placebo for about six months.

In the vaccine arm researchers observed T-cell responses that were significantly higher than those with placebo. T-cells play a critical part in immunity to foreign substances. No vaccine-related serious adverse events were observed.

Prof Mark Hatherill, director at SA Tuberculosis Vaccine Initiative at UCT said: “These results tell us that ID93 + GLA-SE should be tested at the end of treatment as a vaccine to prevent recurrent TB. The next logical step is to test whether the vaccine can be given earlier during TB treatment to improve treatment outcomes.”

A vaccine which can prevent the recurrence of TB in people who have recovered from it could potentially be an important control strategy. Recurrence of TB after treatment is a significant contributor to the disease burden in endemic settings such as SA. According to the latest research in SA, rates of TB recurrence increased by almost nine-fold in the past 13 years irrespective of HIV status.

According to a study done jointly by the Desmond Tutu TB Centre at UCT and the University of Amsterdam, the rate of recurrent TB was 16.4 per 1,000 person-years and increased per subsequent episode 8.4-fold, from 14.6 to 122.7 per 1,000 from episode 2 to episode 6, respectively. Researchers observed similar increases when results were stratified according to HIV status.

Worldwide, SA has the third-highest incidence of TB after India and China, and new cases increased 400% over the past 15 years. Out of the 500,000 TB cases in SA it is estimated that 330,000, or 66%, of people have both HIV and TB.

Researchers argue that recurrent disease is a major limiting factor in efforts to shorten and simplify the six-month standard treatment course for drug-sensitive TB and the longer and more toxic treatment regimens for drug-resistant TB. A vaccine that lowers rates of disease recurrence might allow shorter and less toxic TB treatment regimens.

Prof Rhea Coler, senior investigator at the Seattle Children’s Hospital, who is part of the TB vaccine study, said the latest results had laid groundwork for follow-on studies to evaluate the vaccine as a therapeutic adjunct to antibiotic treatment in people with both drug-sensitive and drug-resistant TB.

Prof Tom Scriba also from SATVI at UCT noted that TB patients typically already have substantial levels of T-cell responses to the TB germ. It was not known if vaccination after the TB was cured would be capable of modulating or boosting these pre-existing T- cell responses.

“The ID93 + GLA-SE vaccine boosted T-cell responses to much higher levels than were present before vaccination, while it also induced high levels of antibody responses. These responses persisted at high levels until the end of the trial follow up, which is an encouraging result.”

Follow-up trials designed to test the efficacy of the vaccine would be needed to determine if these immune responses are capable of protecting against recurrent TB disease.