Shen Yan, Wang Jun, Huang Yuxiao, Liang Jiao, Liu Xuewu, Wu Dudu, Jiang He, Zhao Ya, Li Yinghui
Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
Student Brigade Five-Year Clinical Speciality, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
Parasitol Res. 2016 May;115(5):1907-13. doi: 10.1007/s00436-016-4931-7. Epub 2016 Jan 30.
Malaria is a severe, life-threatening infectious disease that endangers human health. However, there are no vaccines or immune strategy of vaccines succeeding in both erythrocytic and pre-erythrocytic stage. During the liver stage of the Plasmodium life cycle, sporozoites invade the host liver cells. The sporozoites, then, induce a cellular immune response via the major histocompatibility complex (MHC) molecules on their surfaces. The cytotoxic T lymphocytes (CTLs) then recognize the corresponding antigen-MHC complex on the surfaces of these infected liver cells and kill them. However, dominant epitopes with high MHC affinity are prone to mutation due to immune selection pressure. CTLs evoked by the original dominant epitopes cannot recognize the mutated epitopes, leading to immune evasion. In this study, we have modified the cryptic epitopes of different antigens in the sporozoite and liver stages of Plasmodium falciparum to increase their immunogenicity without changing T cell antigen receptor (TCR)-peptide binding specificity. In addition, we have also added an important erythrocytic phase protective antigen, named apical membrane antigen 1 (AMA-1), to this process with the goal of constructing a complex multi-stage, multi-epitope recombinant DNA vaccine against P. falciparum. The vaccine was tested in HHD-2 mice. The method involved multiple stages of the P. falciparum life cycle as well as elucidation both humoral and cellular immunity. The conclusion drawn from the study was that the vaccine might provide an important theoretical and practical basis for generating effective preventative or therapeutic vaccine against P. falciparum.
疟疾是一种严重的、危及生命的传染病，危害人类健康。然而，目前尚无在红细胞期和红细胞前期均成功的疫苗或疫苗免疫策略。在疟原虫生命周期的肝脏阶段，子孢子侵入宿主肝细胞。然后，子孢子通过其表面的主要组织相容性复合体（MHC）分子诱导细胞免疫反应。细胞毒性T淋巴细胞（CTL）随后识别这些受感染肝细胞表面相应的抗原-MHC复合体并将其杀死。然而，由于免疫选择压力，具有高MHC亲和力的显性表位容易发生突变。由原始显性表位诱发的CTL无法识别突变后的表位，从而导致免疫逃逸。在本研究中，我们对恶性疟原虫子孢子和肝脏阶段不同抗原的隐蔽表位进行了修饰，以提高其免疫原性，同时不改变T细胞抗原受体（TCR）-肽结合特异性。此外，我们还在此过程中添加了一种重要的红细胞期保护性抗原，即顶膜抗原1（AMA-1），目的是构建一种针对恶性疟原虫的复杂多阶段、多表位重组DNA疫苗。该疫苗在HHD-2小鼠中进行了测试。该方法涉及恶性疟原虫生命周期的多个阶段，以及对体液免疫和细胞免疫的阐明。该研究得出的结论是，该疫苗可能为开发针对恶性疟原虫的有效预防性或治疗性疫苗提供重要的理论和实践基础。
