Sadoff J C, Ballou W R, Baron L S, Majarian W R, Brey R N, Hockmeyer W T, Young J F, Cryz S J, Ou J, Lowell G H
Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Science. 1988 Apr 15;240(4850):336-8. doi: 10.1126/science.3281260.
Immunization with radiation-attenuated malaria sporozoites induces potent cellular immune responses, but the target antigens are unknown and have not previously been elicited by subunit vaccines prepared from the circumsporozoite (CS) protein. A method is described here for inducing protective cell-mediated immunity to sporozoites by immunization with attenuated Salmonella typhimurium transformed with the Plasmodium berghei CS gene. These transformants constitutively express CS antigens and, when used to immunize mice orally, colonize the liver, induce antigen-specific cell-mediated immunity, and protect mice against sporozoite challenge in the absence of antisporozoite antibodies. These data indicate that the CS protein contains T cell epitopes capable of inducing protective cell-mediated immunity, and emphasize the importance of proper antigen presentation in generating this response. Analogous, orally administered vaccines against human malaria might be feasible.
用辐射减毒的疟原虫子孢子进行免疫可诱导强烈的细胞免疫反应，但靶抗原未知，且以前由环子孢子（CS）蛋白制备的亚单位疫苗未曾引发过这种反应。本文描述了一种通过用携带伯氏疟原虫CS基因的减毒鼠伤寒沙门氏菌进行免疫来诱导对疟原虫子孢子的保护性细胞介导免疫的方法。这些转化体组成性表达CS抗原，当用于口服免疫小鼠时，它们定殖于肝脏，诱导抗原特异性细胞介导免疫，并在没有抗子孢子抗体的情况下保护小鼠免受子孢子攻击。这些数据表明CS蛋白含有能够诱导保护性细胞介导免疫的T细胞表位，并强调了适当的抗原呈递在产生这种反应中的重要性。类似地，口服给药的抗人类疟疾疫苗可能是可行的。
