Heterologous mRNA-protein vaccination with Tc24 induces a robust cellular immune response against Trypanosoma cruzi , characterized by an increased level of polyfunctional CD8 + T-cells.

Autor:	Poveda C; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Leão AC; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Mancino C; Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX, USA.; Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, USA., Taraballi F; Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX, USA.; Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, USA., Chen YL; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Adhikari R; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Villar MJ; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Kundu R; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Nguyen DM; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA., Versteeg L; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA.; Cell Biology and Immunology Group, Wageningen University & Research, the Netherlands., Strych U; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Hotez PJ; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.; Department of Biology, Baylor University, Waco, TX, USA., Bottazzi ME; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.; Department of Biology, Baylor University, Waco, TX, USA., Pollet J; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA., Jones KM; Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
Jazyk:	angličtina
Zdroj:	Current research in immunology [Curr Res Immunol] 2023 Jul 20; Vol. 4, pp. 100066. Date of Electronic Publication: 2023 Jul 20 (Print Publication: 2023).
DOI:	10.1016/j.crimmu.2023.100066
Abstrakt:	Tc24 is a Trypanosoma cruzi- derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi . This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with either the Tc24-C4 protein + glucopyranosyl A (GLA)-squalene emulsion, Tc24 mRNA Lipid Nanoparticles, or with heterologous protein/mRNA or mRNA/protein combinations, respectively. Two weeks after the last vaccination, mice were euthanized, spleens were collected to measure antigen-specific T-cell responses, and sera were collected to evaluate IgG titers and isotypes. Heterologous presentation of the Tc24 antigen generated antigen-specific polyfunctional CD8 + T cells, a balanced Th1/Th2/Th17 cytokine profile, and a balanced humoral response with increased serum IgG, IgG1 and IgG2c antibody responses. We conclude that heterologous vaccination using Tc24 mRNA to prime and Tc24-C4 protein to boost induces a broad and robust antigen-specific immune response that was equivalent or superior to two doses of a homologous protein vaccine, the homologous mRNA vaccine and the heterologous Tc24-C4 Protein/mRNA vaccine. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Institutional reports financial support was provided by 10.13039/100012394Robert J Kleberg Jr and Helen C Kleberg Foundation. All Authors are part of a team of scientists advancing research towards the development of a therapeutic Chagas disease vaccine. MEB and PJH are listed among the inventors on a Chagas disease vaccine patent, submitted by Baylor College of Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the review article apart from those disclosed. (© 2023 The Authors.)
Databáze:	MEDLINE
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