title: A therapeutic nanoparticle vaccine against Trypanosoma cruzi in a BALB/c mouse model of Chagas disease.
abstract: Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNγ-producing splenocytes, IgG2a titers, and proliferative capacity of CD8(+) T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.
authors.affiliation: a Interdepartmental Program in Translational Biology and Molecular Medicine , Baylor College of Medicine , Houston , TX , USA.|b Medical Scientist Training Program, Baylor College of Medicine , Houston , TX , USA.|c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.
authors.forename: Meagan A
authors.initials: MA
authors.lastname: Barry
authors.affiliation: c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.|d National School of Tropical Medicine, Baylor College of Medicine , Houston , TX , USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Jones
authors.affiliation: a Interdepartmental Program in Translational Biology and Molecular Medicine , Baylor College of Medicine , Houston , TX , USA.|c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.|d National School of Tropical Medicine, Baylor College of Medicine , Houston , TX , USA.|h Department of Molecular Virology and Microbiology , Baylor College of Medicine , Houston , TX , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Heffernan
authors.affiliation: e Summer Medical and Research Training Program, Baylor College of Medicine , Houston , TX , USA.
authors.forename: Munir H
authors.initials: MH
authors.lastname: Buhaya
authors.affiliation: c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.
authors.forename: Coreen M
authors.initials: CM
authors.lastname: Beaumier
authors.affiliation: c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Keegan
authors.affiliation: c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhan
authors.affiliation: f Laboratorio de Parasitología, Centro de Investigaciones Regionales Dr Hideyo Noguchi, Universidad Autónoma de Yucatán , Mérida , Mexico.|g Department of Tropical Medicine , School of Public Health and Tropical Medicine, Tulane University , New Orleans , LA , USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Dumonteil
authors.affiliation: a Interdepartmental Program in Translational Biology and Molecular Medicine , Baylor College of Medicine , Houston , TX , USA.|c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.|d National School of Tropical Medicine, Baylor College of Medicine , Houston , TX , USA.|h Department of Molecular Virology and Microbiology , Baylor College of Medicine , Houston , TX , USA.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bottazzi
authors.affiliation: a Interdepartmental Program in Translational Biology and Molecular Medicine , Baylor College of Medicine , Houston , TX , USA.|c Department of Pediatrics , Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine , Houston , TX , USA.|d National School of Tropical Medicine, Baylor College of Medicine , Houston , TX , USA.|h Department of Molecular Virology and Microbiology , Baylor College of Medicine , Houston , TX , USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000628:therapy; D014355:Chagas Disease / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000469:parasitology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D018512:Parasitemia / Q000628:therapy; D016052:Protozoan Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma
keywords: Trypanosoma cruzi; chagas disease; immunotherapy; nanoparticle vaccine; parasite; therapeutic vaccine