title: A synthetic peptide from Trypanosoma cruzi mucin-like associated surface protein as candidate for a vaccine against Chagas disease.
abstract: Chagas disease, caused by Trypanosoma cruzi, is responsible for producing significant morbidity and mortality throughout Latin America. The disease has recently become a public health concern to nonendemic regions like the U.S. and Europe. Currently there are no fully effective drugs or vaccine available to treat the disease. The mucin-associated surface proteins (MASPs) are glycosylphosphatidylinositol (GPI)-anchored glycoproteins encoded by a multigene family with hundreds of members. MASPs are among the most abundant antigens found on the surface of the infective trypomastigote stage of T. cruzi, thus representing an attractive target for vaccine development. Here we used immunoinformatics to select a 20-mer peptide with several predicted overlapping B-cell, MHC-I, and MHC-II epitopes, from a MASP family member expressed on mammal-dwelling stages of T. cruzi. The synthetic MASP peptide conjugated to keyhole limpet hemocyanin (MASPpep-KLH) was tested in presence or not of an adjuvant (alum, Al) as a vaccine candidate in the C3H/HeNsd murine model of T. cruzi infection. In considerable contrast to the control groups receiving placebo, Al, or KLH alone or the group immunized with MASPpep-KLH/Al, the group immunized with MASPpep-KLH showed 86% survival rate after challenge with a highly lethal dose of trypomastigotes. As evaluated by quantitative real-time polymerase chain reaction, MASPpep-KLH-immunized animals had much lower parasite load in the heart, liver, and spleen than control animals. Moreover, protected animals produced trypanolytic, protective antibodies, and a cytokine profile conducive to resistance against parasite infection. Finally, in vivo depletion of either CD4(+) or CD8(+) T cells indicated that the latter are critical for protection in mice immunized with MASPpep-KLH. In summary, this new peptide-based vaccine with overlapping B- and T-cell epitopes is able to control T. cruzi infection in mice by priming both humoral and cellular immunity.
authors.affiliation: Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, United States.
authors.forename: Carylinda
authors.initials: C
authors.lastname: Serna
authors.affiliation: Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, United States.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lara
authors.affiliation: Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, United States.
authors.forename: Silas P
authors.initials: SP
authors.lastname: Rodrigues
authors.affiliation: Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, United States; Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Alexandre F
authors.initials: AF
authors.lastname: Marques
authors.affiliation: Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, United States. Electronic address: icalmeida@utep.edu.
authors.forename: Igor C
authors.initials: IC
authors.lastname: Almeida
authors.affiliation: Border Biomedical Research Center, Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, United States. Electronic address: ramaldonado@utep.edu.
authors.forename: Rosa A
authors.initials: RA
authors.lastname: Maldonado
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D056724:Immunity, Humoral; D008562:Membrane Glycoproteins / Q000276:immunology; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009077:Mucins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D014349:Trypanosoma cruzi; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; D009077:Mucins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic
keywords: Chagas disease; Immunoinformatics; Proteomics; Trypanosoma cruzi; Vaccine