title: A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors.
abstract: Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi's amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the "Antigen Capsid-Incorporation" strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. afarrow@uab.edu.
authors.forename: Anitra L
authors.initials: AL
authors.lastname: Farrow
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jbpb43@uab.edu.
authors.forename: Binghao J
authors.initials: BJ
authors.lastname: Peng
authors.affiliation: Division of Pulmonary, Allergy and Critical Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. linlingu_yz@hotmail.com.
authors.forename: Linlin
authors.initials: L
authors.lastname: Gu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. akrend@uab.edu.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Krendelchtchikov
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. qlm@uab.edu.|Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA. qlm@uab.edu.
authors.forename: Qiana L
authors.initials: QL
authors.lastname: Matthews
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D004337:Drug Carriers; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D007111:Immunity, Cellular; D051379:Mice; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D004337:Drug Carriers; D000939:Epitopes; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C493236:ASP-2 protein, Trypanosoma cruzi; D009439:Neuraminidase
keywords: Chagas’ disease; Trypanosoma cruzi; adenovirus serotype 48; amastigote surface protein-2; antigen capsid-incorporation; gp83; vaccine