title: Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease.
abstract: BACKGROUND
  Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope ofTrypanosoma cruzi(T. cruzi)trypomastigote gp83 (Ad5-gp83) provided immunoprotection againstT. cruziinfection. The purpose of this work was to design an improved vaccine forT. cruziusing a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of theT. cruziamastigote surface protein 2.
  
  
  METHODS
  Protein IX (pIX)-modified Ad vector (Ad5-pIX-ASP-M) was generated, characterized, and validated. C3H/He mice were immunized with Ad5-pIX-ASP-M and Ad5-gp83 and the cell-mediated responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and intracellular staining. Immunized mice were challenged withT. cruzito evaluate the vaccine efficacy.
  
  
  RESULTS
  Our findings indicate that Ad5-pIX-ASP-M was viable. Specific CD8+T-cell mediated responses prior to the challenge show an increase in IFNγand TNFαproduction. A single immunization with Ad5-pIX-ASP-M provided protection fromT. cruziinfection, but co-immunizations with Ad5-pIX-ASP-M and Ad5-gp83 provided a higher immunoprotection and increased survival rate of mice.
  
  
  CONCLUSIONS
  Overall, these results suggest that the combination of gp83 and ASP-M specific epitopes onto the capsid-incorporated adenoviruses would provide superior protection against Chagas disease as compared with Ad5-gp83 alone.
authors.affiliation: Department of Biological Sciences, Alabama State University, Montgomery, AL; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL.
authors.forename: Qiana L
authors.initials: QL
authors.lastname: Matthews
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL.
authors.forename: Anitra L
authors.initials: AL
authors.lastname: Farrow
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, TN.
authors.forename: Girish
authors.initials: G
authors.lastname: Rachakonda
authors.affiliation: Division of Pulmonary, Allergy and Critical Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Linlin
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, TN.
authors.forename: Pius
authors.initials: P
authors.lastname: Nde
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Krendelchtchikov
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, TN.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Pratap
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, TN.
authors.forename: Shruti S
authors.initials: SS
authors.lastname: Sakhare
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL.
authors.forename: Steffanie
authors.initials: S
authors.lastname: Sabbaj
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, TN.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lima
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, TN.
authors.forename: Fernando
authors.initials: F
authors.lastname: Villalta
keywords: Chagas disease; T. cruzi vaccine constructs; amastigote surface protein 2 epitope; co-immunization; epitope-capsid incorporation; immunoprotection; trypomastigote gp83 neutralizing epitope