Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed M. vaccae administered daily for one month

Abstract

ObjectiveImmunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed Mycobacterium vaccae (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct.MethodsThe outcome of Phase III trial of V7 containing 10 µg of hydrolyzed M. vaccae was evaluated in 152 patients randomized at 2:1 ratio: V7 (N = 100), placebo (N = 52). Both arms received conventional 1st or 2nd line TB drugs co-administered with daily pill of V7 or placebo.ResultsAfter one month mycobacterial clearance was observed in 68% (P < 0.0001) and 23.1% (P = 0.04) of patients on V7 and placebo. Stratified conversion rates in V7 recipients with drug-sensitive and multidrug-resistant TB were 86.7% and 55.6% vs 27.2% and 15% in placebo. Patients on V7 gained on average 2.4 kg (P < 0.0001) vs 0.3 kg (P = 0.18) in placebo. Improvements in hemoglobin levels, erythrocyte sedimentation rate and leukocyte counts were significantly better than in controls. Liver function tests revealed that V7 can prevent chemotherapy-induced hepatic damage.ConclusionOral M. vaccae is safe, can overcome TB-associated weight loss and inflammation, reduce hepatotoxicity of TB drugs, improve sputum conversion three-fold OR 3.15; 95%CI (2.3,4.6), and cut treatment length by at least six-fold. Longer follow-up studies might be needed to further substantiate our findings (Clinicaltrials.gov: NCT01977768).

Rapidly Growing Mycobacterium Species: The Long and Winding Road from Tuberculosis Vaccines to Potent Stress-Resilience Agents

“…TB represents a global health problem that is further aggravated by malnutrition and poor hygiene in developing countries, and is one of the most common co-infections and causes of death among human immunodeficiency virus (HIV)-infected individuals [ 142 ]. Moreover, certain M. tuberculosis strains are known to cause difficult-to-treat infections such as multi-drug-resistant [ 143 ], extremely drug resistant, and totally drug resistant TB [ 96 , 144 ], overall generating high socioeconomic burden [ 43 ]. Therefore, there is a clear unmet need for developing novel and effective drugs for the prevention and treatment of TB.…”

Biovacc-19: A Candidate Vaccine for Covid-19 (SARS-CoV-2) Developed from Analysis of its General Method of Action for Infectivity

“…However, it cannot be used repeatedly because it will induce a nonspecific humoral response that will enhance cancer progression. In an attempt to overcome this limitation, Standford and Rook developed a programme for improved agents that could replace BCG in the control of Tuberculosis and noted that heat killed Mycobacterium vaccae had the ability to enhance TH-1 responses and suppress the humoral response, making it a therapeutic agent in its own right (Bourinbaiar et al, 2019). Further research showed that Mycobacterium obuense was superior to M. vaccae and was much easier to manufacture with good manufacturing practice standards.…”

Update on TB Vaccine Pipeline

“…vaccae ™ vaccine is a lysate comprised of inactivated Mycobacterium vaccae (non-tuberculous mycobacteria) developed as an immunotherapeutic agent to help shorten TB treatment for patients with drug-susceptible TB and licensed by the China Food and Drug Administration (FDA). A Phase III study of efficacy has been recently published [2,62] (Figures 2 and 3).…”

“…Since the majority of the adolescent and adult population in countries endemic of TB has been previously vaccinated with BCG at birth, what is sought with subunit candidates comprising specific Mtb antigens is to potentiate the pre-existing immunity induced by BCG [2, 46,62]. Recent studies indicate that new TB vaccines that are compared to BCG should be interpreted cautiously with reference to a specific BCG formulation and not presumed to generalize to all BCGs [13].…”