Hoffman S L, Doolan D L, Sedegah M, Aguiar J C, Wang R, Malik A, Gramzinski R A, Weiss W R, Hobart P, Norman J A, Margalith M, Hedstrom R C
Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
Vaccine. 1997 Jun;15(8):842-5. doi: 10.1016/s0264-410x(96)00273-3.
Data generated in the Plasmodium yoelii rodent model indicated that plasmid DNA vaccines encoding the P.yoelii circumsporozoite protein (PyCSP) or 17 kDa hepatocyte erythrocyte protein (PyHEP17) were potent inducers of protective CD8+ T cell responses directed against infected hepatocytes. Immunization with a mixture of these plasmids circumvented the genetic restriction of protective immunity and induced additive protection. A third DNA vaccine encoding the P. yoelii sporozoite surface protein 2 (PySSP2) also induced protection. The P. falciparum genes encoding the homologues of these three protective P. yoelii antigens as well as another P. falciparum gene encoding a protein that is expressed in infected hepatocytes have been chosen for the development of a human vaccine. The optimal plasmid constructs for human use will be selected on the basis of immunogenicity data generated in mice and nonhuman primates. We anticipate that optimization of multi-gene P. falciparum DNA vaccines designed to protect against malaria by inducing CD8+ T cells that target infected hepatocytes will require extensive clinical trials during the coming years.
约氏疟原虫啮齿动物模型产生的数据表明，编码约氏疟原虫环子孢子蛋白（PyCSP）或17 kDa肝细胞红细胞蛋白（PyHEP17）的质粒DNA疫苗是针对受感染肝细胞的保护性CD8 + T细胞反应的有效诱导剂。用这些质粒的混合物进行免疫可规避保护性免疫的遗传限制并诱导累加性保护。第三种编码约氏疟原虫子孢子表面蛋白2（PySSP2）的DNA疫苗也可诱导保护作用。已选择编码这三种保护性约氏疟原虫抗原同源物的恶性疟原虫基因以及另一种编码在受感染肝细胞中表达的蛋白质的恶性疟原虫基因来开发人类疫苗。将根据在小鼠和非人类灵长类动物中产生的免疫原性数据选择适合人类使用的最佳质粒构建体。我们预计，在未来几年中，旨在通过诱导靶向受感染肝细胞的CD8 + T细胞来预防疟疾的多基因恶性疟原虫DNA疫苗的优化将需要进行广泛的临床试验。
