COMPLETE SOLUBLE PROTEIN ANTIGEN AS VACCINE AND THERAPEUTICS AGAINST KALA-AZAR

摘要

In this study, it is demonstrated that complete soluble antigen from attenuated leishmania parasite UR6 (CSA-A) is able to confer protection against the experimental challenge of two different virulent strains of L.donovani, pentavalent antimony-sensitive strain AG83, or the pentavalent antimony-resistant strain GE1F8R. Protection induced by CSA-A does not require adjuvant and extends to the control of parasite burden in the spleen, an organ in which low level of parasite usually persists. The high level of IL-12 mRNA detected in spleen cells of animals immunized with CSA-A alone indicated that CSA-A may have inherent TH1 inducing adjuvant property. The CSA-A induced protection was NO mediated, as evidenced by the high levels of iNOS mRNA in mice injected with CSA-A alone. It was further observed that CSA-A priming was also effective in established infection models with 80% mice showing complete absence of parasite in both the spleen and liver. Protection induced by CSA-A is strong and long lasting. It was observed that vaccinated mice that had resolved the primary infection were able to resist a subsequent virulent leishmania challenge. CSA-A confers complete sterile protection in the majority ( 80%) of animals. This extent of formidable protection is hitherto not achieved with any other vaccine composition in absence of an adjuvant. Thus it is shown that CSA-A immunization confers complete protection to both antimony sensitive and resistant strains of Leishmania donovani, in absence of an adjuvant. This result is particularly significant in context of the decreasing efficacy of chemotherapeutic intervention along the face of increased emergence of drug resistant L. donovani strains and might lead to homogeneity in vaccine design against any forms of drug-resistant and drug-susceptible Leishmania strains.