Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: evidence for mixed Th1- and Th2-like responses in visceral leishmaniasis.
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TLDR
This is the first report of a vaccine conferring protection to both antimony responsive and resistant Leishmania strains reflecting several aspects of clinical visceral leishmaniasis.Abstract:
The emergence of an increasing number of Leishmania donovani strains resistant to pentavalent antimonials (SbV), the first line of treatment for visceral leishmaniasis worldwide, accounts for decreasing efficacy of chemotherapeutic interventions A kinetoplastid membrane protein-11 (KMP-11)-encoding construct protected extremely susceptible golden hamsters from both pentavalent antimony responsive (AG83) and antimony resistant (GE1F8R) virulent L donovani challenge All the KMP-11 DNA vaccinated hamsters continued to survive beyond 8 mo postinfection, with the majority showing sterile protection Vaccinated hamsters showed reversal of T cell anergy with functional IL-2 generation along with vigorous specific anti-KMP-11 CTL-like response Cytokines known to influence Th1- and Th2-like immune responses hinted toward a complex immune modulation in the presence of a mixed Th1/Th2 response in conferring protection against visceral leishmaniasis KMP-11 DNA vaccinated hamsters were protected by a surge in IFN-γ, TNF-α, and IL-12 levels along with extreme down-regulation of IL-10 Surprisingly the prototype candidature of IL-4, known as a disease exacerbating cytokine, was found to have a positive correlation to protection Contrary to some previous reports, inducible NO synthase was actively synthesized by macrophages of the protected hamsters with concomitant high levels of NO production This is the first report of a vaccine conferring protection to both antimony responsive and resistant Leishmania strains reflecting several aspects of clinical visceral leishmaniasisread more
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Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model.
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Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4+ T Cells
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Vaccines for leishmaniasis in the fore coming 25 years.
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Failure of Pentavalent Antimony in Visceral Leishmaniasis in India: Report from the Center of the Indian Epidemic
Shyam Sundar,Deepak K. More,Manoj Kumar Singh,Vijay P. Singh,Sashi Sharma,Anand Makharia,Prasanna C. K. Kumar,Henry W. Murray +7 more
TL;DR: In India, 320 patients with visceral leishmaniasis received identical pentavalent antimony (Sb) treatment, and Sb induced long-term cure in 35% of those in Bihar versus 86% (95% CI, 79%-93%) of Those in Uttar Pradesh.
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Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase.
Michael U. Shiloh,John D. MacMicking,Susan C. Nicholson,Juliet E. Brause,Strite Potter,Michael W. Marino,Ferric C. Fang,Mary C. Dinauer,Carl Nathan +8 more
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