title: Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.
abstract: Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1.
authors.affiliation: Southwest Electronic Energy Medical Research Institute, Stafford, TX, USA; Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Knight
authors.forename: B
authors.initials: B
authors.lastname: Zingales
authors.forename: M E
authors.initials: ME
authors.lastname: Bottazzi
authors.forename: P
authors.initials: P
authors.lastname: Hotez
authors.forename: B
authors.initials: B
authors.lastname: Zhan
mesh_terms: D000940:Antigenic Variation; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D016052:Protozoan Vaccines / Q000737:chemistry / Q000276:immunology*; D014349:Trypanosoma cruzi; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000276:immunology
chemical_list: D000939:Epitopes; D016052:Protozoan Vaccines; D014643:Variant Surface Glycoproteins, Trypanosoma; C070842:trypomastigote specific surface antigen
keywords: CD8+ T lymphocytes; MHC; Trypanosoma spp.; chagas disease; polymorphism; vaccination