AI Article Synopsis
- Multi-drug resistant tuberculosis (MDR-TB) and extremely drug resistant TB (XDR-TB) are significant global health issues, prompting the development of innovative therapeutic vaccines like HSP65-vaccine, granulysin-vaccine, and Ksp37-vaccine.
- The HSP65-vaccine demonstrated a strong therapeutic effect against both MDR-TB and XDR-TB in mice, with intradermal immunization being more effective than other methods, and achieving enhanced results when combined with the antibiotic Isoniazid.
- Research on Ksp37 and granulysin vaccines in transgenic mice showed resistance to TB infection, highlighting the potential of combining DNA vaccines or using them alongside antibiotics
Article Abstract
Purpose: Multi-drug resistant tuberculosis (MDR-TB) and extremely drug resistant (XDR) TB are big problems in the world. We have developed novel TB therapeutic vaccines, HVJ-Envelope/HSP65 + IL-12 DNA vaccine (HSP65-vaccine), granulysin vaccine and killer specific secretory protein of 37kDa (Ksp37) vaccine.
Methods And Results: HSP65 vaccine showed strong therapeutic effect against both MDR-TB and XDR-TB in mice. Intradermal immunization of HSP65-vaccine showed stronger therapeutic effect against TB than intramuscular or subcutaneous immunization. Furthermore, the synergistic therapeutic effect was observed when the vaccine was administrated in combination with Isoniazid (INH), which is a first line drug for chemotherapy. The combination of types of vaccines (HSP65- and granulysin- vaccines) also showed synergistic therapeutic effect. In the monkey model, granulysin-vaccine prolonged the survival period after the infection of TB and long-term survival was observed in vaccine-treated group. We examined the potential of two kinds of novel DNA vaccines (Ksp37-vaccine and granulysin-vaccine). Both vaccines augmented in vivo differentiation of CTL against TB. We measured the amount of Ksp37 protein in human serum and revealed that the level of Ksp37 protein of patients with tuberculosis was lower than that of healthy volunteers. Therefore, we established Ksp37 transgenic mice as well as granulysin transgenic mice to elucidate the function of those proteins. Both transgenic mice were resistant to TB infection.
Conclusion: These data indicate the potential of combinational therapy; the combination of two DNA vaccines or combination of DNA vaccine with antibiotic drug. Thus, it will provide a novel strategy for the treatment of MDR-TB.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891708 | PMC |
| http://dx.doi.org/10.4161/hv.23230 | DOI Listing |
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