title: Photodynamic vaccination of hamsters with inducible suicidal mutants of Leishmania amazonensis elicits immunity against visceral leishmaniasis.
abstract: Leishmania, naturally residing in the phagolysosomes of macrophages, is a suitable carrier for vaccine delivery. Genetic complementation of these trypanosomatid protozoa to partially rectify their defective heme-biosynthesis renders them inducible with delta-aminolevulinate to develop porphyria for selective photolysis, leaving infected host cells unscathed. Delivery of released "vaccines" to antigen-presenting cells is thus expected to enhance immune response, while their self-destruction presents added advantages of safety. Such suicidal L. amazonensis was found to confer immunoprophylaxis and immunotherapy on hamsters against L. donovani. Neither heat-killed nor live parasites without suicidal induction were effective. Photodynamic vaccination of hamsters with the suicidal mutants reduced the parasite loads by 99% and suppressed the development of disease. These suppressions were accompanied by an increase in Leishmania-specific delayed-type hypersensitivity and lymphoproliferation as well as in the levels of splenic iNOS, IFN-gamma, and IL-12 expressions and of Leishmania-specific IgG2 in the serum. Moreover, a single intravenous administration of T cells from vaccinated hamsters was shown to confer on naïve animals an effective cellular immunity against L. donovani challenges. The absence of lesion development at vaccination sites and parasites in the draining lymphnodes, spleen and liver further indicates that the suicidal mutants provide a safe platform for vaccine delivery against experimental visceral leishmaniasis.
authors.affiliation: Division of Parasitology, Central Drug Research Institute, Lucknow, India.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Kumari
authors.forename: Mukesh
authors.initials: M
authors.lastname: Samant
authors.forename: Prashant
authors.initials: P
authors.lastname: Khare
authors.forename: Pragya
authors.initials: P
authors.lastname: Misra
authors.forename: Sujoy
authors.initials: S
authors.lastname: Dutta
authors.forename: Bala Krishna
authors.initials: BK
authors.lastname: Kolli
authors.forename: Sharad
authors.initials: S
authors.lastname: Sharma
authors.forename: Kwang Poo
authors.initials: KP
authors.lastname: Chang
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
mesh_terms: D019264:Adoptive Transfer; D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D006224:Cricetinae; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D007891:Leishmania / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000627:therapeutic use*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009154:Mutation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011165:Porphyrinogens / Q000276:immunology; D012867:Skin / Q000469:parasitology / Q000473:pathology; D013601:T-Lymphocytes / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D054332:Leishmaniasis Vaccines; D017319:Photosensitizing Agents; D011165:Porphyrinogens; D000622:Aminolevulinic Acid