ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease
Julia Castro, Rory Cristiane Fortes de Brito, Natália Satchiko Hojo-Souza, Bárbara Azevedo, Natalia Salazar, Camila Pontes Ferreira, Caroline Junqueira, Ana Paula Fernandes, R. C. S. Vasconcellos, Jamille M. Cardoso, Rodrigo Dian de Oliveira Aguiar‐Soares, Paula Melo de Abreu Vieira, Cláudia Martins Carneiro, Bruno Vinícius Santos Valiate, C. Z. P. de Toledo, Andres Μ. Salazar, Otávia L. Caballero, Joseli Lannes-Vieira, Santuza R. Teixeira, Alexandre Barbosa Reis, Ricardo T. Gazzinelli
Abstract
Abstract Immunization 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.