Abstract
BackgroundImmunotherapy to enhance the efficiency of the immune response in tuberculosis patients and to eliminate the persisters could be an additional valuable strategy to complement anti-mycobacterial chemotherapy. This study was designed to assess the immunotherapeutic potential of Ag85B as an adjunct to chemotherapy and its effect against active and persister bacteria left after therapy in mouse model of tuberculosis.Methods6-8 week old female Balb/c mice were infected with Mycobacterium tuberculosis and treated with chemotherapy or immunotherapy. Protective efficacy was measured in terms of bacterial counts in lungs and spleen. Immune correlates of protection in terms of Th1 and Th2 cytokines were measured by ELISA.ResultsTherapeutic effect of Ag85B was found to be comparable to that of short term dosage of antituberculous drugs (ATDs). The therapeutic effect of ATDs was augmented by the simultaneous treatment with rAg85B and moreover therapy with this protein allowed us to reduce ATD dosage. This therapy was found to be effective even in case of drug persisters. The levels of antigen specific IFNγ and IL-12 were significantly increased after immunotherapy as compared to the basal levels; moreover antigen specific IL-4 levels were depressed on immunotherapy with Ag85B.ConclusionWe demonstrated in this study that the new combination approach using immunotherapy and concurrent chemotherapy should offer several improvements over the existing regimens to treat tuberculosis. The therapeutic effect is associated not only with initiating a Th1 response but also with switching the insufficient Th2 immune status to the more protective Th1 response.
Highlights
Immunotherapy to enhance the efficiency of the immune response in tuberculosis patients and to eliminate the persisters could be an additional valuable strategy to complement anti-mycobacterial chemotherapy
Immunotherapy to enhance the efficiency of the immune response in M. tuberculosis infected patients could be an additional valuable strategy to complement anti-bacterial chemotherapy
Therapeutic effect of the Ag85B protein and its DNA vaccine Mice infected with the M. tuberculosis H37Rv strain were treated with either rAg85B protein or Ag85B-DNA (Figure 1), and the therapeutic effects were expressed as the bacterial load in the spleen and lung (Figure 2 & Table 1)
Summary
Immunotherapy to enhance the efficiency of the immune response in tuberculosis patients and to eliminate the persisters could be an additional valuable strategy to complement anti-mycobacterial chemotherapy. Major obstacle in control of tuberculosis being poor patient compliance with the protracted regimen in areas with limited resources which may lead to relapse of active disease, transmission of infection and development of drug resistant strains [1]. In such circumstances, immunotherapy to enhance the efficiency of the immune response in M. tuberculosis infected patients could be an additional valuable strategy to complement anti-bacterial chemotherapy. Several studies have shown a significant protective effect in the lungs of mice immunized with Ag85B [13,14,15,16], whereas a few contradictory reports on the efficacy of
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