期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 1, 页码 178-191出版社
WILEY
DOI: 10.1002/eji.200838389
关键词
Porphyrinogenic mutant; Suicidal vaccination; T-cell-adoptive transfer; Visceral leishmaniasis
类别
资金
- USA-NIH [Al-68835]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI068835] Funding Source: NIH RePORTER
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-amino-levulinate 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 naive 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.
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