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Pathog Immun. 2016 Fall-Winter;1(2):214-233.

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

Author information

1
Department of Biological Sciences, Alabama State University, Montgomery, AL; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL.
2
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, AL.
3
Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, TN.
4
Division of Pulmonary, Allergy and Critical Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.

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.

KEYWORDS:

Chagas disease; T. cruzi vaccine constructs; amastigote surface protein 2 epitope; co-immunization; epitope-capsid incorporation; immunoprotection; trypomastigote gp83 neutralizing epitope

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