Clinicians are trying a leprosy vaccine to help relapsing tuberculosis (TB) patients fight the infection for good1.
Known as Immuvac, the vaccine was developed to prevent leprosy. But the vaccine agent, Mycobacterium indicus pranii , displays antigens similar to both the leprosy bacterium and the TB bacterium. These antigens create an immune response that helps clear TB from patients’ lungs — and when combined with the Revised National Tuberculosis Control Programme-Directly Observed Treatment, Short-course (RNTCP-DOTS), effectively cure patients who are already resistant to first line TB therapies.
“We had no idea how many doses of vaccine would be required, so we planned on giving more,” said Rajni Rani, a superannuated senior scientist at the National Institute for Immunology and an author of the study. “We started seeing results much faster than anticipated, so while the dose was kept the same, the number of injections and the schedule was altered to check if we could expedite the clearance.”
About one quarter of people globally infected with TB reside in India, and the country has seen a rise of MDR TB cases in the past several years.
The multi-centre clinical trial targeted patients with previous high exposure to antibiotics, either as a result of defaulting during previous treatment or relapsing after completing the standard treatment. Known as Category II patients, these groups are at greater risk for developing MDR TB. Additionally, the study evaluated whether adding the vaccine could shorten treatment time, because the current lengthy treatment makes patients less likely to complete the full course of antibiotics, raising concern for cultivating MDR or extensively drug resistant (XDR) TB.
By four weeks, 67% of patients who were receiving the adjunct vaccine had sputum culture converted, whereas only 57% of the placebo group had converted. In subsequent follow up visits, the vaccinated group continued to have higher rates of conversion. Though the final cure rate between vaccine and placebo was not significant, a striking 100% patients who were already resistant to two or three drugs and who received the vaccine were cured, compared to 76% of those who received the placebo.
“Since it worked best in the more difficult to treat cases, we hope it should work in MDR cases as well,” said Rani, adding that another trial would be needed. Though researchers expect that a vaccine immunotherapy effective against susceptible TB would also protect against drug resistant forms, “Use of any vaccine puts pressure on a pathogen to mutate to escape immune pressure,” said Daniel Hoft, the principal investigator of the Saint Louis University Vaccine & Treatment Evaluation Unit, who was not involved with the study.
More data is needed to validate these cure rates, however, as cured patients were ultimately identified through a sputum smear test — even though the sputum culture conversion test is the only endpoint so far that has reliably predicted TB treatment success or failure. “It is problematic that the researchers studying Mycobacterium inidcus pranii used microscopic smear negative conversion as their main definition for ‘cure’,” said Hoft. “If you do not use the right definitions, you can't compare to other studies.”
Patient recruitment for experimental TB therapy trials can be difficult since patients are concerned about delaying the standard of care treatment while trying something new. However, the enrollment in this study was robust because the injections were given as an adjunct, at the same time as antibiotics. “This is not, ‘first try and then do that,’” said Rohit Sarin, the director of the National Institute of Tuberculosis and Respiratory Diseases, and an author of the study.
Mycobacterium indicus pranii is named for its discoverer and birthplace Pran Talwar at the National Institute of Immunology, and developed by Cadila Pharmaceuticals in Ahmedabad. The trial results came just weeks after a pilot programme launched in Gujarat and Bihar for vaccinating people in leprosy remission.