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首页> 外文期刊>Vaccine >Successful vaccination against Leishmania donovani infection in Indian langur using alum-precipitated autoclaved Leishmania major with BCG
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Successful vaccination against Leishmania donovani infection in Indian langur using alum-precipitated autoclaved Leishmania major with BCG

机译:使用明矾沉淀的高压灭菌的利什曼原虫伴BCG成功接种印度叶猴中的利什曼原虫感染疫苗

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Autoclaved Leishmania major (ALM) along with BCG, presently undergoing phase II clinical trial by WHO for its vaccine potential against cutaneous leishmaniasis, has been successfully evaluated in single and triple dose schedules against L. donovani in Indian langurs (Presbytis entellus). Encouraged with the results, another formulation alum-precipitated ALM (provided by WHO) along with BCG has been evaluated in this system. Eight monkeys were vaccinated with alum-precipitated ALM + BCG (1 mg of each per animal) while four were kept as unvaccinated controls. All were challenged with 100 x 10(6) amastigotes i.v. on day 60 post vaccination. Parasitic assessment in splenic tissue was performed on day 45, 90 and 180 p.c. Initially, seven of the eight vaccinated monkeys developed infection (two to six amastigotes per 1000 cell nuclei), which resolved by day 180 p.c., while the eighth monkey had a parasite burden of 14 amastigotes per 1000 cell nuclei on day 45 p.c. and died on day 130 p.c. On the other hand, there was progressive infection in unvaccinated control animals and three out of four died between days 110 and 120 p.c., and one monkey, which had low parasite burden, died on day 178 p.c. Prior to challenge, there was an initial rise in antileishmanaial antibodies in the vaccinated group compared to the unvaccinated control group, which later came down to normal level, while it remained higher in the unvaccinated control group. An increasing pattern of antigen-specific proliferative responses and interferon-gamma level to the two antigens - autoclaved L. donovani (ALD) and ALM - was observed in vaccinated monkeys throughout the experiment. There was a good correlation between parasite burden and IFN-gamma level on days 90 and 180 p.c., indicating IFN-gamma response as a sensitive parameter of immune status. The findings suggest alum-precipitated ALM + BCG as a potential vaccine against visceral leishmaniasis and warrants clinical trials.
机译:高压灭菌的利什曼原虫主要成分(ALM)和卡介苗目前正在接受WHO的针对皮肤利什曼原虫病的疫苗潜力的II期临床试验,已成功针对印度叶猴(Presbytis entellus)单倍剂量和三倍剂量的杜氏利什曼原虫进行了评估。在结果的鼓舞下,在该系统中对另一种明矾沉淀的ALM(由WHO提供)和卡介苗进行了评估。给八只猴子接种明矾沉淀的ALM + BCG(每只动物每只1毫克),而四只作为未接种的对照。所有人均接受100 x 10(6)amastigotes i.v.攻击。接种后第60天。在脾脏第45、90和180天进行了寄生虫评估。最初,八只接种疫苗的猴子中有七只发展成感染(每1000个细胞核有2至6个变形虫),到了第180天就解决了,而第八只猴子在第45天有寄生虫负担,每1000个细胞核中有14个变形虫。于公元130日逝世另一方面,在未接种疫苗的对照动物中有进行性感染,四分之三的死者在110至120天之间死亡,一只寄生虫负担低的猴子死于178天。在攻击之前,与未接种的对照组相比,接种组的抗疟疾抗体最初升高,后来下降到正常水平,而未接种的对照组仍然较高。在整个实验过程中,在接种疫苗的猴子中观察到对两种抗原-高压灭菌的多诺尼乳酸菌(ALD)和ALM的抗原特异性增殖反应和干扰素-γ水平的升高模式。在第90天和180天时,寄生虫负担与IFN-γ水平之间存在良好的相关性,表明IFN-γ反应是免疫状态的敏感参数。研究结果表明,明矾沉淀的ALM + BCG是潜在的抗内脏利什曼病的疫苗,值得临床试验。

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