Ellis J, Ozaki L S, Gwadz R W, Cochrane A H, Nussenzweig V, Nussenzweig R S, Godson G N
Nature. 1983 Apr 7;302(5908):536-8. doi: 10.1038/302536a0.
The malarial sporozoite, the infective stage found in the salivary gland of the insect vector, bears highly immunogenic surface antigen(s). Repeated exposure to irradiated sporozoites induces protection against malaria in several host species, including man. Further, monoclonal antibodies that confer passive immunity react with the immunogenic surface determinants of different sporozoite species. One approach to prevent malaria, therefore, would be to produce a vaccine that induces high titres of circulating antibodies against the sporozoite surface determinant(s). However, production of such a vaccine has not been possible since sporozoites cannot be cultivated in vitro and, therefore, only limited amounts of surface antigen may be obtained. To overcome this problem, we have prepared mRNA from Plasmodium knowlesi-infected mosquitoes to construct a cDNA library. From this library we have isolated a clone that expresses the sporozoite surface antigen as a beta-lactamase fusion protein in the plasmid pBR322. This is the first potentially protective malarial antigen to be cloned by recombinant DNA technology.
疟原虫子孢子是在昆虫媒介唾液腺中发现的感染阶段,带有高度免疫原性的表面抗原。反复接触经辐射的子孢子可使包括人类在内的多种宿主产生抗疟疾保护作用。此外,具有被动免疫作用的单克隆抗体可与不同子孢子物种的免疫原性表面决定簇发生反应。因此,预防疟疾的一种方法是生产一种能诱导产生高滴度循环抗体以对抗子孢子表面决定簇的疫苗。然而,由于子孢子无法在体外培养,因此只能获得有限量的表面抗原,所以无法生产这样的疫苗。为克服这一问题,我们从感染诺氏疟原虫的蚊子中制备了mRNA,以构建一个cDNA文库。从该文库中,我们分离出一个克隆,它在质粒pBR322中作为β-内酰胺酶融合蛋白表达子孢子表面抗原。这是通过重组DNA技术克隆的第一个具有潜在保护作用的疟原虫抗原。