Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
Department of Global Health, University of Washington, Seattle, WA 98195, USA.
Sci Transl Med. 2017 Jan 4;9(371). doi: 10.1126/scitranslmed.aad9099.
Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52/p36/sap1). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers. Pf GAP3KO sporozoites were delivered to 10 volunteers using infected mosquito bites with a single exposure consisting of 150 to 200 bites per subject. All subjects remained blood stage-negative and developed inhibitory antibodies to sporozoites. GAP3KO rodent malaria parasites engendered complete, protracted immunity against infectious sporozoite challenge in mice. The results warrant further clinical testing of Pf GAP3KO and its potential development into a vaccine strain.
用整个疟原虫孢子进行人体免疫可提供针对疟疾感染的完全、绝育性免疫。然而，在保持整个寄生虫疫苗免疫原性的同时实现一致的安全性仍然是一个艰巨的挑战。我们通过缺失在红细胞前期表达的三个基因（Pf p52/p36/sap1）生成了一种遗传减毒的恶性疟原虫（Pf）疟原虫。然后，我们在人类志愿者中测试了这种遗传工程化（Pf GAP3KO）孢子的安全性和免疫原性。用感染的蚊子叮咬将 Pf GAP3KO 孢子传递给 10 名志愿者，每个受试者单次暴露包含 150 到 200 个蚊子叮咬。所有受试者均保持血期阴性，并对孢子产生抑制性抗体。GAP3KO 啮齿动物疟原虫在小鼠中引发完全、持久的抗传染性孢子挑战免疫。这些结果证明 Pf GAP3KO 值得进一步临床测试，并有可能开发成疫苗株。
