title: Polymorphism in liver-stage malaria vaccine candidate proteins: immune evasion and implications for vaccine design.
abstract: The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses 'surgical strike' strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes.
authors.affiliation: a Vaccine and Infectious Diseases Laboratory, Department of Immunology , Monash University , Melbourne , VIC , Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.affiliation: a Vaccine and Infectious Diseases Laboratory, Department of Immunology , Monash University , Melbourne , VIC , Australia.
authors.forename: Kirsty L
authors.initials: KL
authors.lastname: Wilson
authors.affiliation: a Vaccine and Infectious Diseases Laboratory, Department of Immunology , Monash University , Melbourne , VIC , Australia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D019943:Amino Acid Substitution; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D017780:Malaria Vaccines / Q000276:immunology* / Q000302:isolation & purification; D010961:Plasmodium / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins
keywords: Malaria; antagonism; antigen; cross-reactivity; immune evasion; immune interference; polymorphism; pre-erythrocytic; vaccine