Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease.

Academic Article

Abstract

  • BACKGROUND: Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of Trypanosoma cruzi (T. cruzi) trypomastigote gp83 (Ad5-gp83) provided immunoprotection against T. cruzi infection. The purpose of this work was to design an improved vaccine for T. cruzi using 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 the T. cruzi amastigote 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 with T. cruzi to 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 IFNγ and TNFα production. A single immunization with Ad5-pIX-ASP-M provided protection from T. cruzi infection, 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.
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    Keywords

  • Chagas disease, T. cruzi vaccine constructs, amastigote surface protein 2 epitope, co-immunization, epitope-capsid incorporation, immunoprotection, trypomastigote gp83 neutralizing epitope
  • Digital Object Identifier (doi)

    Author List

  • Matthews QL; Farrow AL; Rachakonda G; Gu L; Nde P; Krendelchtchikov A; Pratap S; Sakhare SS; Sabbaj S; Lima MF
  • Start Page

  • 214
  • End Page

  • 233
  • Volume

  • 1
  • Issue

  • 2