Immunization with the DNA-Encoding N-Terminal Domain of Proteophosphoglycan of Leishmania donovani Generates Th1-Type Immunoprotective Response against Experimental Visceral Leishmaniasis
| Autor: | Pramod K. Kushawaha, Pragya Misra, Amogh A. Sahasrabuddhe, Mukesh Samant, Prashant Khare, Shraddha Kumari, Reema Gupta, Anuradha Dube |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Immunology Protozoan Proteins Leishmania donovani Biology Leishmania mexicana Cell Line DNA vaccination Cricetinae parasitic diseases Escherichia coli Vaccines DNA medicine Animals Humans Immunology and Allergy Leishmania major Amastigote Leishmaniasis Vaccines Mesocricetus Cell Polarity Membrane Proteins DNA Protozoan Th1 Cells medicine.disease biology.organism_classification Leishmania Virology Peptide Fragments Protein Structure Tertiary Visceral leishmaniasis Leishmaniasis Visceral Proteoglycans |
| Zdroj: | The Journal of Immunology. 183:470-479 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0900265 |
| Popis: | Leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (PPGs) which exist as secretory as well as surface-bound forms in both promastigotes and amastigotes. The structure and function of PPGs have been reported to be species and stage specific as in the case of Leishmania major and Leishmania mexicana; there has been no such information available for Leishmania donovani. We have recently demonstrated that PPG is differentially expressed in sodium stibogluconate-sensitive and -resistant clinical isolates of L. donovani. To further elucidate the structure and function of the ppg gene of L. donovani, a partial sequence of its N-terminal domain of 1.6 kb containing the majority of antigenic determinants, was successfully cloned and expressed in prokaryotic as well as mammalian cells. We further evaluated the DNA-encoding N-terminal domain of the ppg gene as a vaccine in golden hamsters (Mesocricetus auratus) against the L. donovani challenge. The prophylactic efficacy to the tune of ∼80% was observed in vaccinated hamsters and all of them could survive beyond 6 mo after challenge. The efficacy was supported by a surge in inducible NO synthase, IFN-γ, TNF-α, and IL-12 mRNA levels along with extreme down-regulation of TGF-β, IL-4, and IL-10. A rise in the level of Leishmania-specific IgG2 was also observed which was indicative of enhanced cellular immune response. The results suggest the N-terminal domain of L. donovani ppg as a potential DNA vaccine against visceral leishmaniasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|