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
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 s...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Immunology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590255523000124 |
| _version_ | 1827609521191649280 |
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| author | Cristina Poveda Ana Carolina Leão Chiara Mancino Francesca Taraballi Yi-Lin Chen Rakesh Adhikari Maria Jose Villar Rakhi Kundu Duc M. Nguyen Leroy Versteeg Ulrich Strych Peter J. Hotez Maria Elena Bottazzi Jeroen Pollet Kathryn M. Jones |
| author_facet | Cristina Poveda Ana Carolina Leão Chiara Mancino Francesca Taraballi Yi-Lin Chen Rakesh Adhikari Maria Jose Villar Rakhi Kundu Duc M. Nguyen Leroy Versteeg Ulrich Strych Peter J. Hotez Maria Elena Bottazzi Jeroen Pollet Kathryn M. Jones |
| author_sort | Cristina Poveda |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T07:34:37Z |
| format | Article |
| id | doaj.art-c7749e7404fb460eb9e2b9e33a987dc5 |
| institution | Directory Open Access Journal |
| issn | 2590-2555 |
| language | English |
| last_indexed | 2024-03-09T07:34:37Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Immunology |
| spelling | doaj.art-c7749e7404fb460eb9e2b9e33a987dc52023-12-03T05:42:49ZengElsevierCurrent Research in Immunology2590-25552023-01-014100066Heterologous mRNA-protein vaccination with Tc24 induces a robust cellular immune response against Trypanosoma cruzi, characterized by an increased level of polyfunctional CD8+ T-cellsCristina Poveda0Ana Carolina Leão1Chiara Mancino2Francesca Taraballi3Yi-Lin Chen4Rakesh Adhikari5Maria Jose Villar6Rakhi Kundu7Duc M. Nguyen8Leroy Versteeg9Ulrich Strych10Peter J. Hotez11Maria Elena Bottazzi12Jeroen Pollet13Kathryn M. Jones14Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USA; Corresponding author. Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USACenter for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX, USA; Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, USACenter for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX, USA; Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, USADepartment of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USADepartment of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USADepartment of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USADepartment of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USADepartment of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USADepartment 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 NetherlandsDepartment of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USADepartment 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, USADepartment 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, USADepartment of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital Center for Vaccine Development, Houston, TX, USADepartment 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, USATc24 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.http://www.sciencedirect.com/science/article/pii/S2590255523000124Chagas diseaseImmunogenicity |
| spellingShingle | Cristina Poveda Ana Carolina Leão Chiara Mancino Francesca Taraballi Yi-Lin Chen Rakesh Adhikari Maria Jose Villar Rakhi Kundu Duc M. Nguyen Leroy Versteeg Ulrich Strych Peter J. Hotez Maria Elena Bottazzi Jeroen Pollet Kathryn M. Jones 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 Current Research in Immunology Chagas disease Immunogenicity |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Chagas disease Immunogenicity |
| url | http://www.sciencedirect.com/science/article/pii/S2590255523000124 |
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