Photodynamic vaccination of hamsters with inducible suicidal mutants of Leishmania amazonensis elicits immunity against visceral leishmaniasis.
Photodynamic vaccination of hamsters with inducible suicidal mutants of Leishmania amazonensis elicits immunity against visceral leishmaniasis.
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DOI：
10.1002/eji.200838389
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发表时间：
2009-01
影响因子：
5.4
通讯作者：
Dube, Anuradha
中科院分区：
文献类型：
--
作者：
Kumari, Shraddha;Samant, Mukesh;Khare, Prashant;Misra, Pragya;Dutta, Sujoy;Kolli, Bala Krishna;Sharma, Sharad;Chang, Kwang Poo;Dube, Anuradha
天然存在于巨噬细胞的吞噬溶酶体中的利什曼原虫是用于疫苗递送的合适载体。这些锥虫原生动物的遗传互补部分纠正了它们有缺陷的血红素生物合成，使它们能够被δ-氨基乙酰丙酸诱导产生卟啉病，用于选择性光解，使受感染的宿主细胞毫发无损。因此，将释放的“疫苗”递送到抗原呈递细胞预期会增强免疫应答，而它们的自我破坏呈现出额外的安全优势。真想自杀amazonensis具有免疫预防和免疫治疗作用。donovani。无论是热杀死或活的寄生虫没有自杀诱导是有效的。光动力接种仓鼠的自杀突变体减少了99%的寄生虫负荷，抑制疾病的发展。这些补充伴随着利什曼特异性迟发型超敏反应和淋巴细胞增殖以及脾iNOS、IFN-γ和IL-12表达水平和血清中利什曼特异性IgG 2水平的增加。此外，单次静脉注射接种仓鼠的T细胞可使未接种动物产生有效的抗L.多诺万的挑战。在疫苗接种部位和引流淋巴结、脾脏和肝脏中没有病变发展进一步表明自杀突变体为针对实验性内脏利什曼病的疫苗递送提供了安全的平台。
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 δ-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-γ 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.
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影响因子：
2.7
作者：
Convit, J
通讯作者：
Convit, J
影响因子：
3.1
作者：
Breton, M;Tremblay, MJ;Papadopoulou, B
通讯作者：
Papadopoulou, B
影响因子：
82.9
作者：
Brockstedt, DG;Bahjat, KS;Dubensky, TW
通讯作者：
Dubensky, TW
影响因子：
5.5
作者：
Bhowmick, Sudipta;Ravindran, Rajesh;Ali, Nahid
通讯作者：
Ali, Nahid
DOI：
10.1098/rstb.1984.0111
发表时间：
1984-01-01
影响因子：
6.3
作者：
HOWARD, JG;LIEW, FY
通讯作者：
LIEW, FY