Immunological Basis for the Introduction of Immunotherapy with Mycobacterium Vaccae into the Routine Treatment of TB

Abstract

An account is given of the immunological investigations carried out in Rosario (Argentina) to identify suitable methods for the assessment of the efficacy of immunotherapy for TB. Some of these were then applied to three small studies: one of a single injected dose of heat-killed, borate-buffered Mycobacterium vaccae administered early in treatment, another of three such doses administered at monthly intervals from the start of treatment, and the third of ten oral doses at frequent intervals throughout short-course chemotherapy. All three displayed better clearance of bacilli from the sputum, faster improvement in clinical symptoms, better radiological resolution of lesions and a return of most immunological parameters towards those of healthy persons. In principle, the immune change achieved is an increase in Th1 mechanisms, notably IL-2 and -12 with downregulation of the tissue damaging aspects of Th2. As an addition to chemotherapy for drug-susceptible or drug-resistant TB, with or without concomitant HIV infection, this immunotherapy offers a safe and effective improvement.

Efficacy of Mycobacterium indicus pranii Immunotherapy as an Adjunct to Chemotherapy for Tuberculosis and Underlying Immune Responses in the Lung

“…Interestingly the immunotherapeutic activity of M.vaccae has been shown to be mediated by the strong Th1 immune response viz. IL-2 and IL-12 and the concurrent downregulation of Th2 response [58] which was also observed with MIP immunotherapy in our study. However, a comprehensive clinical trial is required to finally conclude the immunotherapeutic efficacy of MIP.…”

Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice

“…The immunotherapy with rBCG-LTAK63 can be further combined with conventional antibiotics aiming at reducing the time of chemotherapy required. Other immunotherapeutic strategies commonly used include vaccines in association with chemotherapy ( 5 – 7 , 21 – 23 ). Importantly, these candidates demonstrate increased Th1 responses also as prophylactic vaccines ( 24 – 26 ).…”

Totally drug‐resistant tuberculosis and adjunct therapies

“…Unfortunately, none is directed specifically at, or being tested in the context of, MDR‐/XDR‐/TDR‐TB. TB vaccines that have reached clinical trials comprise either inactivated forms of M.tb , that is, RUTI or mycobacteria other than TB, such as Mycobacterium indicus pranii or Mycobacteria vaccae . The vaccine based on M. vaccae consists of heat‐killed bacteria and has been shown to promote an immune Th1 response , whereas the RUTI vaccine consists of detoxified fragments of antigens associated with M.tb latency.…”