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Immunotherapeutic role of Ag85B as an adjunct to antituberculous chemotherapy.

Sheikh JA, Khuller GK, Verma I - J Immune Based Ther Vaccines (2011)

Bottom Line: Therapeutic effect of Ag85B was found to be comparable to that of short term dosage of antituberculous drugs (ATDs).This therapy was found to be effective even in case of drug persisters.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. induvermabio@gmail.com.

ABSTRACT

Background: 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. 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.

Methods: 6-8 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.

Results: Therapeutic 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.

Conclusion: We 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.

No MeSH data available.


Related in: MedlinePlus

Effect of immunotherapy on persisters in terms of Log10 CFUs of Mtb at two weeks post treatment in the lungs and spleen of Mtb infected animals. Two weeks post challenge with Mtb, mice were treated with ATD for 4 weeks and then 4 doses of rAg85B weekly. Two weeks post treatment lungs and spleen from M. tuberculosis H37Rv infected animals were isolated and cultured on Middlebrook 7H11 agar plates. Results are expressed as mean log10 CFUs ± standard deviation of 5 animals per group tested individually. Statistical analysis of the results was carried out by Student's t test. ***p< 0.001, compared to animals that were left untreated during the treatment period of eight weeks. #p< 0.05, compared to animals receiving ATD for four weeks. (ATD: Antituberculous Drugs; IT: Immunotherapy; O/W: Once Weekly)
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Figure 3: Effect of immunotherapy on persisters in terms of Log10 CFUs of Mtb at two weeks post treatment in the lungs and spleen of Mtb infected animals. Two weeks post challenge with Mtb, mice were treated with ATD for 4 weeks and then 4 doses of rAg85B weekly. Two weeks post treatment lungs and spleen from M. tuberculosis H37Rv infected animals were isolated and cultured on Middlebrook 7H11 agar plates. Results are expressed as mean log10 CFUs ± standard deviation of 5 animals per group tested individually. Statistical analysis of the results was carried out by Student's t test. ***p< 0.001, compared to animals that were left untreated during the treatment period of eight weeks. #p< 0.05, compared to animals receiving ATD for four weeks. (ATD: Antituberculous Drugs; IT: Immunotherapy; O/W: Once Weekly)

Mentions: After the completion of conventional chemotherapy, the bacteria that survive are usually persisters and in order to check the efficacy of current immunotherapy on those persisters, mice were administered a four week dose of chemotherapy to eliminate the drug susceptible bacteria and then were subjected to immunotherapy. Significant reduction in bacterial CFUs was observed as compared to group where mice were adjuvant immunized for 1 month after chemotherapy; implying that immunotherapy with Ag85B protein was effective in inhibiting the persisters to regrow, that could resist the 'short term' chemotherapy (Figure 3).


Immunotherapeutic role of Ag85B as an adjunct to antituberculous chemotherapy.

Sheikh JA, Khuller GK, Verma I - J Immune Based Ther Vaccines (2011)

Effect of immunotherapy on persisters in terms of Log10 CFUs of Mtb at two weeks post treatment in the lungs and spleen of Mtb infected animals. Two weeks post challenge with Mtb, mice were treated with ATD for 4 weeks and then 4 doses of rAg85B weekly. Two weeks post treatment lungs and spleen from M. tuberculosis H37Rv infected animals were isolated and cultured on Middlebrook 7H11 agar plates. Results are expressed as mean log10 CFUs ± standard deviation of 5 animals per group tested individually. Statistical analysis of the results was carried out by Student's t test. ***p< 0.001, compared to animals that were left untreated during the treatment period of eight weeks. #p< 0.05, compared to animals receiving ATD for four weeks. (ATD: Antituberculous Drugs; IT: Immunotherapy; O/W: Once Weekly)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3142482&req=5

Figure 3: Effect of immunotherapy on persisters in terms of Log10 CFUs of Mtb at two weeks post treatment in the lungs and spleen of Mtb infected animals. Two weeks post challenge with Mtb, mice were treated with ATD for 4 weeks and then 4 doses of rAg85B weekly. Two weeks post treatment lungs and spleen from M. tuberculosis H37Rv infected animals were isolated and cultured on Middlebrook 7H11 agar plates. Results are expressed as mean log10 CFUs ± standard deviation of 5 animals per group tested individually. Statistical analysis of the results was carried out by Student's t test. ***p< 0.001, compared to animals that were left untreated during the treatment period of eight weeks. #p< 0.05, compared to animals receiving ATD for four weeks. (ATD: Antituberculous Drugs; IT: Immunotherapy; O/W: Once Weekly)
Mentions: After the completion of conventional chemotherapy, the bacteria that survive are usually persisters and in order to check the efficacy of current immunotherapy on those persisters, mice were administered a four week dose of chemotherapy to eliminate the drug susceptible bacteria and then were subjected to immunotherapy. Significant reduction in bacterial CFUs was observed as compared to group where mice were adjuvant immunized for 1 month after chemotherapy; implying that immunotherapy with Ag85B protein was effective in inhibiting the persisters to regrow, that could resist the 'short term' chemotherapy (Figure 3).

Bottom Line: Therapeutic effect of Ag85B was found to be comparable to that of short term dosage of antituberculous drugs (ATDs).This therapy was found to be effective even in case of drug persisters.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. induvermabio@gmail.com.

ABSTRACT

Background: 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. 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.

Methods: 6-8 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.

Results: Therapeutic 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.

Conclusion: We 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.

No MeSH data available.


Related in: MedlinePlus