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

• Main Authors: Qiana L. Matthews (Author), Anitra L. Farrow (Author), Girish Rachakonda (Author), Linlin Gu (Author), Pius Nde (Author), Alexandre Krendelchtchikov (Author), Siddarth Pratap (Author), Shruti S. Sakhare (Author), Steffanie Sabbaj (Author), Maria F. Lima (Author), Fernando Villalta (Author)
• Format: Book
• Published: Case Western Reserve University, 2016-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2469-2964
10.20411/pai.v1i2.114