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恒河猴经辐射后的疟原虫孢子免疫应答与保护效果。

Immune responses and protection of Aotus monkeys immunized with irradiated Plasmodium vivax sporozoites.

机构信息

Instituto de Inmunología, Universidad del Valle, Cali, Colombia.

出版信息

Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):43-50. doi: 10.4269/ajtmh.2011.09-0759.

Abstract

A non-human primate model for the induction of protective immunity against the pre-erythrocytic stages of Plasmodium vivax malaria using radiation-attenuated P. vivax sporozoites may help to characterize protective immune mechanisms and identify novel malaria vaccine candidates. Immune responses and protective efficacy induced by vaccination with irradiated P. vivax sporozoites were evaluated in malaria-naive Aotus monkeys. Three groups of six monkeys received two, five, or ten intravenous inoculations, respectively, of 100,000 irradiated P. vivax sporozoites; control groups received either 10 doses of uninfected salivary gland extract or no inoculations. Immunization resulted in the production low levels of antibodies that specifically recognized P. vivax sporozoites and the circumsporozoite protein. Additionally, immunization induced low levels of antigen-specific IFN-γ responses. Intravenous challenge with viable sporozoites resulted in partial protection in a dose-dependent manner. These findings suggest that the Aotus monkey model may be able to play a role in preclinical development of P. vivax pre-erythrocytic stage vaccines.

摘要

使用辐照衰减的间日疟原虫孢子虫诱导针对间日疟原虫红细胞前期的保护性免疫的非人类灵长类动物模型,可能有助于阐明保护性免疫机制和鉴定新的疟疾疫苗候选物。在无疟疾的食蟹猴中评估了用辐照间日疟原虫孢子虫接种诱导的免疫应答和保护效力。三组各六只猴子分别接受两次、五次或十次静脉内接种 100,000 个辐照间日疟原虫孢子虫;对照组接受 10 剂未感染的唾液腺提取物或不接种。免疫接种导致产生了低水平的特异性识别间日疟原虫孢子虫和环子孢子蛋白的抗体。此外,免疫接种诱导了低水平的抗原特异性 IFN-γ 反应。静脉内用活孢子虫进行攻击,结果表明剂量依赖性地部分保护。这些发现表明,食蟹猴模型可能能够在间日疟原虫红细胞前期疫苗的临床前开发中发挥作用。

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