Immunization with a recombinant ASP-2/Transialidase chimeric protein induces robust protective immunity in both murine and canine models of Chagas’ disease
Research Square (Research Square)(2022)
摘要
Abstract We have systematically shown that the Amastigote Surface Protein-2 (ASP-2) and Transialidase (TS) antigens either in the form of recombinant protein or encoded in the plasmids and human adenovirus 5 (hAd5) confer strong protection against different lineages of Trypanosoma cruzi parasites. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from ASP-2 and TS (DTT-1) and evaluated its efficacy in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Our results show that mice immunized with DTT-1 protein together with Poly-ICLC (Hiltonol) become highly resistant to challenge with the Y strain of 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 and an equivalent level of protection induced by the DNA/hAd5 protocol. DTT-1 induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was mediated by B lymphocytes, CD8 T cells and IFNγ. Finally, we evaluated the toxicity, immunogenicity and efficacy of the DTT-1 and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated to 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 formulations protected dogs against challenge with the Berenice strain of T. cruzi. Despite to the similar efficacy, we conclude that moving ahead with DTT-1 together with Hiltonol is advantageous over the hAd5 vaccine due to the cost-benefit for development and large-scale production.
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关键词
chagas disease,asp-2/transialidase chimeric protein,robust protective immunity
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