title: Analysis of the immune response of a new malaria vaccine based on the modification of cryptic epitopes.
abstract: 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.
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Student Brigade Five-Year Clinical Speciality, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Dudu
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China. zhaoya@fmmu.edu.cn.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China. yinghlzb@fmmu.edu.cn.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000235:genetics*; D004912:Erythrocytes; D007111:Immunity, Cellular; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D051379:Mice; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D034101:Sporozoites / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000939:Epitopes; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic
keywords: Cryptic epitope; Malaria vaccine; Multi-epitope
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