Project Lead(s): Allen Bain
According to the World Health Organization’s 2015 Report, tuberculosis (TB) is now killing more people each year than the AIDS virus. However, current TB drugs are not very effective, particularly against multidrug-resistant TB (MDR-TB) or against TB with HIV, which requires 24–36 months of treatment rather than usual 6–9 months for drug-sensitive TB.
Drugs against MDR-TB are far more expensive and drug toxicity is another major concern that makes patients quit before they are cured. Safe, affordable and faster-acting interventions represent an unmet medical need.
This project was a follow-up to earlier work and involved conducting a clinical trial with an oral, tableted formulation of heat-killed Mycobacterium vaccae (V7) as an adjunct immunotherapy treatment for TB. The team previously developed this product, which drastically reduced the duration of treatment, producing sputum clearance in an overwhelming majority of TB patients in as short a time as one month.
A double-blinded, placebo-controlled Phase III trial was conducted, using the TB vaccine containing 10 μg of V7. The trial was undertaken with 152 patients randomized at a 2:1 ratio. Both study arms received conventional first- or second-line anti-TB chemotherapy, administered along with a daily pill of V7 or placebo. The subject population had four categories of TB, distributed in both V7 and placebo arms: (1) drug-sensitive TB; (2) multi-drug-resistant TB; (3) TB with HIV, and (4) extensively drug-resistant TB (XDR).
Trial results demonstrated that daily oral M. vaccae can be safely used as an adjunct therapy with TB treatment, to improve patient outcomes. After one month, mycobacterial clearance in sputum smears was observed in 68% and 23.1% of patients on V7 and placebo respectively, a significant difference. Sputum conversion correlated with weight gain among V7 recipients, i.e., 2.4 kg (P<0.0001) versus 0.3 kg (P=0.18) in the control group.
The improvement in hemoglobin levels, erythrocyte sedimentation rate and leukocyte counts was significantly better than in the placebo, indicative of potent, anti-inflammatory activity of V7. Daily treatment with V7 also prevented chemotherapy-induced hepatic damage, as shown by liver function tests.
From these findings, the research team concluded that the low-dose daily oral M. vaccae was safe and has potential as an adjunct immunotherapy targeting the mucosal immunity to overcome TB-associated weight loss and inflammation, reduce hepatotoxicity of TB drugs, improve three-fold the sputum conversion rate and shorten treatment duration of standard TB therapy by at least six-fold.
Compared to available TB chemotherapy treatments, V7 has produced very compelling results that the team feels are better than any other drugs currently under investigation.
The team have been able to register V7 as an immune supplement with health authorities in Mongolia and Ukraine and they plan to seek funding to begin to market the product.
Trial results were presented for the first time at the Global Vaccinology conference in London, UK, on November 25–31, 2016.