ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease
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Published:2023-05-31
Issue:1
Volume:8
Page:
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ISSN:2059-0105
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Container-title:npj Vaccines
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language:en
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Short-container-title:npj Vaccines
Author:
Castro Julia T., Brito RoryORCID, Hojo-Souza Natalia S.ORCID, Azevedo Bárbara, Salazar Natalia, Ferreira Camila P., Junqueira CarolineORCID, Fernandes Ana Paula, Vasconcellos Ronnie, Cardoso Jamille M., Aguiar-Soares Rodrigo D. O., Vieira Paula M. A., Carneiro Cláudia M., Valiate Bruno, Toledo Cristiane, Salazar Andres M., Caballero Otávia, Lannes-Vieira Joseli, Teixeira Santuza R., Reis Alexandre B.ORCID, Gazzinelli Ricardo T.ORCID
Abstract
AbstractImmunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Infectious Diseases,Pharmacology,Immunology
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