Scheller L F, Azad A F
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201, USA.
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4066-8. doi: 10.1073/pnas.92.9.4066.
Immunization of rodents and humans with irradiation-attenuated malaria sporozoites confers preerythrocytic stage-specific protective immunity to challenge infection. This immunity is directed against intrahepatic parasites and involves T cells and interferon gamma, which prevent development of exoerythrocytic stages and subsequent blood infection. The present study was undertaken to determine how protective immunity is achieved after immunization of rodent hosts with irradiated Plasmodium berghei sporozoites. We present evidence that irradiated parasites persist in hepatocytes of rats and mice for up to 6 months after immunization. A relationship between the persistence of parasites and the maintenance of protective immunity was observed. Protective immunity was abrogated in irradiated-sporozoite-immunized rats following the application of chemotherapy to remove preexisting liver parasites. Additionally, protective immunity against sporozoite challenge was established in rats vaccinated with early and late hepatic stages of irradiated parasites. These results show that irradiation-attenuated sporozoites produce persistent intrahepatic stages in vivo necessary for the induction and maintenance of protective immunity.
用经辐射减毒的疟原虫子孢子对啮齿动物和人类进行免疫接种，可赋予针对感染攻击的红细胞前期特异性保护性免疫。这种免疫针对肝内寄生虫，涉及T细胞和干扰素γ，它们可阻止红细胞外期的发育及随后的血液感染。本研究旨在确定用经辐射的伯氏疟原虫子孢子免疫啮齿动物宿主后，如何实现保护性免疫。我们提供的证据表明，经辐射的寄生虫在免疫接种后可在大鼠和小鼠的肝细胞中持续存在长达6个月。观察到寄生虫的持续存在与保护性免疫的维持之间存在关联。在用化疗清除预先存在的肝脏寄生虫后，经辐射子孢子免疫的大鼠的保护性免疫被消除。此外，在用经辐射寄生虫的早期和晚期肝期接种的大鼠中，建立了针对子孢子攻击的保护性免疫。这些结果表明，经辐射减毒的子孢子在体内产生持续的肝内期，这对于诱导和维持保护性免疫是必要的。
