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由包裹在带正电荷脂质体中的杜氏利什曼原虫抗原引发的佐剂性和保护性免疫。

Adjuvanticity and protective immunity elicited by Leishmania donovani antigens encapsulated in positively charged liposomes.

作者信息

Afrin F, Ali N

机构信息

Leishmania Group, Indian Institute of Chemical Biology, Calcutta.

出版信息

Infect Immun. 1997 Jun;65(6):2371-7. doi: 10.1128/iai.65.6.2371-2377.1997.

Abstract

In the search for a leishmaniasis vaccine, extensive studies of cutaneous leishmaniasis have been carried out. Investigations in this regard with the visceral form are limited. As an initial step in the identification of the protective molecules, leishmanial antigens extracted from the membranes of Leishmania donovani promastigotes, alone or in association with liposomes, were evaluated for their immunogenicity and ability to elicit a protective immune response against challenge infection. Intraperitoneal immunization of hamsters and BALB/c mice with the leishmanial antigens conferred protection against infection with the virulent promastigotes. Encapsulation in positively charged liposomes significantly enhanced the protective efficacy of these antigens. The splenic parasite burden of hamsters was reduced by 97% after 6 months of infection. BALB/c mice exhibited 87 and 81.3% protection in the liver and spleen, respectively, after 4 months of infection. These protected animals elicited profound delayed-type hypersensitivity and increased levels of Leishmania-specific immunoglobulin G (IgG) antibodies. Protection in mice also coincided with elevated levels of IgM and IgA antibodies, which decreased with disease progression in the control-infected animals. Although both IgG1 and IgG2a antibodies were present in the sera of infected mice, IgG1 appeared to be the predominant isotype, suggesting a preferential induction of the Th2 type of immune response over that of Th1. Effective stimulation of all the IgG isotypes, particularly IgG2a, after immunization with liposome encapsulated antigens seems to be responsible for the significant levels of resistance against the disease. Taken together, these data indicate a potential for the liposomal antigens as a vaccine which could trigger both humoral and cell-mediated immune responses.

摘要

在寻找利什曼病疫苗的过程中,已经对皮肤利什曼病进行了广泛研究。关于内脏型利什曼病的这方面研究有限。作为鉴定保护性分子的第一步,对从杜氏利什曼原虫前鞭毛体膜中提取的利什曼原虫抗原单独或与脂质体联合进行了免疫原性评估,以及其引发针对攻击感染的保护性免疫反应的能力评估。用利什曼原虫抗原对仓鼠和BALB/c小鼠进行腹腔免疫可使其免受强毒前鞭毛体感染。封装在带正电荷的脂质体中可显著增强这些抗原的保护效力。感染6个月后,仓鼠脾脏中的寄生虫负荷降低了97%。感染4个月后,BALB/c小鼠在肝脏和脾脏中的保护率分别为87%和81.3%。这些受保护的动物引发了强烈的迟发型超敏反应,并提高了利什曼原虫特异性免疫球蛋白G(IgG)抗体水平。小鼠中的保护作用还与IgM和IgA抗体水平升高同时出现,而在对照感染动物中,这些抗体水平随疾病进展而降低。虽然感染小鼠的血清中同时存在IgG1和IgG2a抗体,但IgG1似乎是主要的同种型,这表明Th2型免疫反应比Th1型免疫反应更易被优先诱导。用脂质体包裹的抗原免疫后有效刺激所有IgG同种型,特别是IgG2a,似乎是对该疾病产生显著抵抗力的原因。综上所述,这些数据表明脂质体抗原作为一种疫苗具有引发体液免疫和细胞介导免疫反应的潜力。

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