Davies D Huw, Duffy Patrick, Bodmer Jean-Luc, Felgner Philip L, Doolan Denise L
University of California, Irvine, CA, USA.
National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
Vaccine. 2015 Dec 22;33(52):7496-505. doi: 10.1016/j.vaccine.2015.09.059. Epub 2015 Oct 1.
Until recently, malaria vaccine development efforts have focused almost exclusively on a handful of well characterized Plasmodium falciparum antigens. Despite dedicated work by many researchers on different continents spanning more than half a century, a successful malaria vaccine remains elusive. Sequencing of the P. falciparum genome has revealed more than five thousand genes, providing the foundation for systematic approaches to discover candidate vaccine antigens. We are taking advantage of this wealth of information to discover new antigens that may be more effective vaccine targets. Herein, we describe different approaches to large-scale screening of the P. falciparum genome to identify targets of either antibody responses or T cell responses using human specimens collected in Controlled Human Malaria Infections (CHMI) or under conditions of natural exposure in the field. These genome, proteome and transcriptome based approaches offer enormous potential for the development of an efficacious malaria vaccine.
直到最近,疟疾疫苗的研发工作几乎完全集中在少数几个已得到充分表征的恶性疟原虫抗原上。尽管来自不同大陆的众多研究人员历经半个多世纪的不懈努力,但成功的疟疾疫苗仍然难以实现。恶性疟原虫基因组测序已揭示出五千多个基因,为系统发现候选疫苗抗原奠定了基础。我们正利用这一丰富的信息来发现可能成为更有效疫苗靶点的新抗原。在此,我们描述了对恶性疟原虫基因组进行大规模筛选的不同方法,以便利用在受控人体疟疾感染(CHMI)中收集的人体样本或在野外自然暴露条件下收集的样本,来识别抗体反应或T细胞反应的靶点。这些基于基因组、蛋白质组和转录组的方法为开发有效的疟疾疫苗提供了巨大潜力。