Efficacy of vaccination with a combination of Leishmania amastigote antigens and the lipid A-analogue ONO-4007 for immunoprophylaxis and immunotherapy against Leishmania amazonensis infection in a murine model of New World cutaneous leishmaniasis
Efficacy of vaccination with a combination of Leishmania amastigote antigens and the lipid A-analogue ONO-4007 for immunoprophylaxis and immunotherapy against Leishmania amazonensis infection in a murine model of New World cutaneous leishmaniasis
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DOI：
10.1016/j.vaccine.2006.03.023
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发表时间：
2006-07-07
期刊：
影响因子：
5.5
通讯作者：
Hashiguchi, Yoshihisa
中科院分区：
文献类型：
--
作者：
Calvopina, Manuel;Barroso, Paola A.;Hashiguchi, Yoshihisa
使用激活Toll样受体4途径的佐剂激活先天免疫对于改善寄生虫疫苗诱导的保护具有巨大潜力。我们研究了含有佐剂合成脂质A-类似物、ONO-4007和亚马逊利什曼原虫抗原的疫苗对利什曼病的保护和治疗作用。ONO-4007与可溶性和膜富集的L.将已感染1 × 10（6）L.亚马逊前鞭毛体（免疫治疗研究）或在用相同感染剂量攻击前（免疫预防研究）。在感染性攻击前接种疫苗的小鼠中，60%控制了利什曼原虫感染（定义为无足垫肿胀和阴性利什曼原虫培养物），而对照组为0%，感染后接种疫苗的小鼠中，40%的感染消退，而对照组为0%。免疫预防和免疫治疗模型中的保护性免疫与IL-12和IFN-γ的蛋白质产生增加相关。这些数据表明，用ONO-4007和L.亚马逊黑热病可能用于预防和治疗利什曼病，并且诱导的保护性免疫与1型细胞因子的产生有关。(c)2006爱思唯尔有限公司版权所有。
Activation of innate immunity using adjuvants that activate Toll-like receptor 4 pathways have great potential for improving the protection induced by parasite vaccines. We investigated protective and therapeutic effects of a vaccine against leishmaniasis containing a combination of an adjuvant synthetic lipid A-analogue, ONO-4007 and Leishmania amazonensis antigens. ONO-4007 was co-injected with soluble and membrane-enriched L. amazonensis-amastigote antigens into BALB/c mice that had either already been infected with 1 x 10(6) L. amazonensis promastigotes (immunotherapy study) or before challenge with the same infectious dose (immunoprophylaxis study). Sixty percent of mice vaccinated before infectious challenge controlled their Leishmania infections - defined by the absence of footpad-swelling and negative Leishmania cultures - compared to 0% of controls, and 40% of mice vaccinated after infection resolved their infections compared to 0% of controls. Protective immunity in both immunoprophylaxis and immunotherapy models was associated with increased protein production of IL-12 and IFN-gamma. These data suggest that vaccination with a combination of ONO-4007 and amastigote antigens of L. amazonensis may be useful for the prevention and treatment of leishmaniasis, and that the protective immunity induced is associated with the production of type-1 cytokines. (c) 2006 Elsevier Ltd. All rights reserved.