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

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...

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Autores principales: Matthews, Qiana L., Farrow, Anitra L., Rachakonda, Girish, Gu, Linlin, Nde, Pius, Krendelchtchikov, Alexandre, Pratap, Siddharth, Sakhare, Shruti S., Sabbaj, Steffanie, Lima, Maria F., Villalta, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pathogens and Immunity 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5046838/
https://www.ncbi.nlm.nih.gov/pubmed/27709126
http://dx.doi.org/10.20411/pai.v1i2.114
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author Matthews, Qiana L.
Farrow, Anitra L.
Rachakonda, Girish
Gu, Linlin
Nde, Pius
Krendelchtchikov, Alexandre
Pratap, Siddharth
Sakhare, Shruti S.
Sabbaj, Steffanie
Lima, Maria F.
Villalta, Fernando
author_facet Matthews, Qiana L.
Farrow, Anitra L.
Rachakonda, Girish
Gu, Linlin
Nde, Pius
Krendelchtchikov, Alexandre
Pratap, Siddharth
Sakhare, Shruti S.
Sabbaj, Steffanie
Lima, Maria F.
Villalta, Fernando
author_sort Matthews, Qiana L.
collection PubMed
description 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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spelling pubmed-50468382016-10-03 Epitope Capsid-Incorporation: A New Effective Approach for Vaccine Development for Chagas Disease Matthews, Qiana L. Farrow, Anitra L. Rachakonda, Girish Gu, Linlin Nde, Pius Krendelchtchikov, Alexandre Pratap, Siddharth Sakhare, Shruti S. Sabbaj, Steffanie Lima, Maria F. Villalta, Fernando Pathog Immun Research Article 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. Pathogens and Immunity 2016-09-15 /pmc/articles/PMC5046838/ /pubmed/27709126 http://dx.doi.org/10.20411/pai.v1i2.114 Text en © Pathogens and Immunity 2016 This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Article
Matthews, Qiana L.
Farrow, Anitra L.
Rachakonda, Girish
Gu, Linlin
Nde, Pius
Krendelchtchikov, Alexandre
Pratap, Siddharth
Sakhare, Shruti S.
Sabbaj, Steffanie
Lima, Maria F.
Villalta, Fernando
Epitope Capsid-Incorporation: A New Effective Approach for Vaccine Development for Chagas Disease
title Epitope Capsid-Incorporation: A New Effective Approach for Vaccine Development for Chagas Disease
title_full Epitope Capsid-Incorporation: A New Effective Approach for Vaccine Development for Chagas Disease
title_fullStr Epitope Capsid-Incorporation: A New Effective Approach for Vaccine Development for Chagas Disease
title_full_unstemmed Epitope Capsid-Incorporation: A New Effective Approach for Vaccine Development for Chagas Disease
title_short Epitope Capsid-Incorporation: A New Effective Approach for Vaccine Development for Chagas Disease
title_sort epitope capsid-incorporation: a new effective approach for vaccine development for chagas disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5046838/
https://www.ncbi.nlm.nih.gov/pubmed/27709126
http://dx.doi.org/10.20411/pai.v1i2.114
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