TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice

Wael Hegazy-Hassan, José Antonio Zepeda-Escobar, Laucel Ochoa-García, J. M.Eloy Contreras-Ortíz, Esvieta Tenorio-Borroto, Alberto Barbabosa-Pliego, José Esteban Aparicio-Burgos, Rigoberto Oros-Pantoja, Bruno Rivas-Santiago, Héctor Díaz-Albiter, Nisha Garg, Juan Carlos Vázquez-Chagoyán

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    The efforts for the development and testing of vaccines against Trypanosoma cruzi infection have increased during the past years. We have designed a TcVac series of vaccines composed of T. cruzi derived, GPI-anchored membrane antigens. The TcVac vaccines have been shown to elicit humoral and cellular mediated immune responses and provide significant (but not complete) control of experimental infection in mice and dogs. Herein, we aimed to test two immunization protocols for the delivery of DNA-prime/DNA-boost vaccine (TcVac1) composed of TcG2 and TcG4 antigens in a BALB/c mouse model. Mice were immunized with TcVac1 through intradermal/electroporation (IDE) or intramuscular (IM) routes, challenged with T. cruzi, and evaluated during acute phase of infection. The humoral immune response was evaluated through the assessment of anti-TcG2 and anti-TcG4 IgG subtypes by using an ELISA. Cellular immune response was assessed through a lymphocyte proliferation assay. Finally, clinical and morphopathological aspects were evaluated for all experimental animals. Our results demonstrated that when comparing TcVac1 IDE delivery vs IM delivery, the former induced significantly higher level of antigen-specific antibody response (IgG2a + IgG2b > IgG1) and lymphocyte proliferation, which expanded in response to challenge infection. Histological evaluation after challenge infection showed infiltration of inflammatory cells (macrophages and lymphocytes) in the heart and skeletal tissue of all infected mice. However, the largest increase in inflammatory infiltrate was observed in TcVac1_IDE/Tc mice when compared with TcVac1_IM/Tc or non-vaccinated/infected mice. The extent of tissue inflammatory infiltrate was directly associated with the control of tissue amastigote nests in vaccinated/infected (vs. non-vaccinated/infected) mice. Our results suggest that IDE delivery improves the protective efficacy of TcVac1 vaccine against T. cruzi infection in mice when compared with IM delivery of the vaccine.

    Original languageEnglish (US)
    Pages (from-to)248-257
    Number of pages10
    JournalVaccine
    Volume37
    Issue number2
    DOIs
    StatePublished - Jan 7 2019

    Fingerprint

    Electroporation
    electroporation
    Trypanosoma cruzi
    Vaccines
    vaccines
    mice
    Infection
    infection
    lymphocyte proliferation
    antigens
    Lymphocytes
    Antigens
    Cellular Immunity
    amastigotes
    recombinant vaccines
    DNA Vaccines
    humoral immunity
    cell-mediated immunity
    Humoral Immunity
    Infection Control

    Keywords

    • Chagas disease
    • Intradermal electroporation
    • Intramuscular
    • Mice model
    • TcVac1
    • Trypanosoma cruzi

    ASJC Scopus subject areas

    • Molecular Medicine
    • Immunology and Microbiology(all)
    • veterinary(all)
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

    Cite this

    Hegazy-Hassan, W., Zepeda-Escobar, J. A., Ochoa-García, L., Contreras-Ortíz, J. M. E., Tenorio-Borroto, E., Barbabosa-Pliego, A., ... Vázquez-Chagoyán, J. C. (2019). TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice. Vaccine, 37(2), 248-257. https://doi.org/10.1016/j.vaccine.2018.11.041

    TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice. / Hegazy-Hassan, Wael; Zepeda-Escobar, José Antonio; Ochoa-García, Laucel; Contreras-Ortíz, J. M.Eloy; Tenorio-Borroto, Esvieta; Barbabosa-Pliego, Alberto; Aparicio-Burgos, José Esteban; Oros-Pantoja, Rigoberto; Rivas-Santiago, Bruno; Díaz-Albiter, Héctor; Garg, Nisha; Vázquez-Chagoyán, Juan Carlos.

    In: Vaccine, Vol. 37, No. 2, 07.01.2019, p. 248-257.

    Research output: Contribution to journalArticle

    Hegazy-Hassan, W, Zepeda-Escobar, JA, Ochoa-García, L, Contreras-Ortíz, JME, Tenorio-Borroto, E, Barbabosa-Pliego, A, Aparicio-Burgos, JE, Oros-Pantoja, R, Rivas-Santiago, B, Díaz-Albiter, H, Garg, N & Vázquez-Chagoyán, JC 2019, 'TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice', Vaccine, vol. 37, no. 2, pp. 248-257. https://doi.org/10.1016/j.vaccine.2018.11.041
    Hegazy-Hassan W, Zepeda-Escobar JA, Ochoa-García L, Contreras-Ortíz JME, Tenorio-Borroto E, Barbabosa-Pliego A et al. TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice. Vaccine. 2019 Jan 7;37(2):248-257. https://doi.org/10.1016/j.vaccine.2018.11.041
    Hegazy-Hassan, Wael ; Zepeda-Escobar, José Antonio ; Ochoa-García, Laucel ; Contreras-Ortíz, J. M.Eloy ; Tenorio-Borroto, Esvieta ; Barbabosa-Pliego, Alberto ; Aparicio-Burgos, José Esteban ; Oros-Pantoja, Rigoberto ; Rivas-Santiago, Bruno ; Díaz-Albiter, Héctor ; Garg, Nisha ; Vázquez-Chagoyán, Juan Carlos. / TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice. In: Vaccine. 2019 ; Vol. 37, No. 2. pp. 248-257.
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    abstract = "The efforts for the development and testing of vaccines against Trypanosoma cruzi infection have increased during the past years. We have designed a TcVac series of vaccines composed of T. cruzi derived, GPI-anchored membrane antigens. The TcVac vaccines have been shown to elicit humoral and cellular mediated immune responses and provide significant (but not complete) control of experimental infection in mice and dogs. Herein, we aimed to test two immunization protocols for the delivery of DNA-prime/DNA-boost vaccine (TcVac1) composed of TcG2 and TcG4 antigens in a BALB/c mouse model. Mice were immunized with TcVac1 through intradermal/electroporation (IDE) or intramuscular (IM) routes, challenged with T. cruzi, and evaluated during acute phase of infection. The humoral immune response was evaluated through the assessment of anti-TcG2 and anti-TcG4 IgG subtypes by using an ELISA. Cellular immune response was assessed through a lymphocyte proliferation assay. Finally, clinical and morphopathological aspects were evaluated for all experimental animals. Our results demonstrated that when comparing TcVac1 IDE delivery vs IM delivery, the former induced significantly higher level of antigen-specific antibody response (IgG2a + IgG2b > IgG1) and lymphocyte proliferation, which expanded in response to challenge infection. Histological evaluation after challenge infection showed infiltration of inflammatory cells (macrophages and lymphocytes) in the heart and skeletal tissue of all infected mice. However, the largest increase in inflammatory infiltrate was observed in TcVac1_IDE/Tc mice when compared with TcVac1_IM/Tc or non-vaccinated/infected mice. The extent of tissue inflammatory infiltrate was directly associated with the control of tissue amastigote nests in vaccinated/infected (vs. non-vaccinated/infected) mice. Our results suggest that IDE delivery improves the protective efficacy of TcVac1 vaccine against T. cruzi infection in mice when compared with IM delivery of the vaccine.",
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