Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes
Dendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, B2T dendrimers displaying two copies of the major type O FMDV antigenic B-cell...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.621537/full |
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| author | Patricia de León Rodrigo Cañas-Arranz Sira Defaus Elisa Torres Mar Forner María J. Bustos Concepción Revilla Javier Dominguez David Andreu Esther Blanco Francisco Sobrino |
| author_facet | Patricia de León Rodrigo Cañas-Arranz Sira Defaus Elisa Torres Mar Forner María J. Bustos Concepción Revilla Javier Dominguez David Andreu Esther Blanco Francisco Sobrino |
| author_sort | Patricia de León |
| collection | DOAJ |
| description | Dendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, B2T dendrimers displaying two copies of the major type O FMDV antigenic B-cell epitope located on the virus capsid [VP1 (140–158)], covalently linked to a heterotypic T-cell epitope from either non-structural protein 3A [3A (21–35)] or 3D [3D (56–70)], named B2T-3A and B2T-3D, respectively, elicit high levels of neutralizing antibodies (nAbs) and IFN-γ-producing cells in pigs. To assess whether the inclusion and orientation of T-3A and T-3D T-cell epitopes in a single molecule could modulate immunogenicity, dendrimers with T epitopes juxtaposed in both possible orientations, i.e., constructs B2TT-3A3D and B2TT-3D3A, were made and tested in pigs. Both dendrimers elicited high nAbs titers that broadly neutralized type O FMDVs, although B2TT-3D3A did not respond to boosting, and induced lower IgGs titers, in particular IgG2, than B2TT-3A3D. Pigs immunized with B2, a control dendrimer displaying two B-cell epitope copies and no T-cell epitope, gave no nABs, confirming T-3A and T-3D as T helper epitopes. The T-3D peptide was found to be an immunodominant, as it produced more IFN-γ expressing cells than T-3A in the in vitro recall assay. Besides, in pigs immunized with the different dendrimeric peptides, CD4+ T-cells were the major subset contributing to IFN-γ expression upon in vitro recall, and depletion of CD4+ cells from PBMCs abolished the production of this cytokine. Most CD4+IFN-γ+ cells showed a memory (CD4+2E3−) and a multifunctional phenotype, as they expressed both IFN-γ and TNF-α, suggesting that the peptides induced a potent Th1 pro-inflammatory response. Furthermore, not only the presence, but also the orientation of T-cell epitopes influenced the T-cell response, as B2TT-3D3A and B2 groups had fewer cells expressing both cytokines. These results help understand how B2T-type dendrimers triggers T-cell populations, highlighting their potential as next-generation FMD vaccines. |
| first_indexed | 2024-12-21T13:08:55Z |
| format | Article |
| id | doaj.art-591c1befb5ff4972aebf55c01b3aa89e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T13:08:55Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-591c1befb5ff4972aebf55c01b3aa89e2022-12-21T19:02:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.621537621537Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell EpitopesPatricia de León0Rodrigo Cañas-Arranz1Sira Defaus2Elisa Torres3Mar Forner4María J. Bustos5Concepción Revilla6Javier Dominguez7David Andreu8Esther Blanco9Francisco Sobrino10Microbes in Health and Welfare Unit, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Madrid, SpainMicrobes in Health and Welfare Unit, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Madrid, SpainDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, SpainCentro de Investigación en Sanidad Animal (CISA-INIA), Madrid, SpainDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, SpainMicrobes in Health and Welfare Unit, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Madrid, SpainDepartamento de Biotecnologı́a, Instituto Nacional de Investigación y Tecnologı́a Agraria y Alimentaria (INIA), Madrid, SpainDepartamento de Biotecnologı́a, Instituto Nacional de Investigación y Tecnologı́a Agraria y Alimentaria (INIA), Madrid, SpainDepartament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, SpainCentro de Investigación en Sanidad Animal (CISA-INIA), Madrid, SpainMicrobes in Health and Welfare Unit, Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Madrid, SpainDendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, B2T dendrimers displaying two copies of the major type O FMDV antigenic B-cell epitope located on the virus capsid [VP1 (140–158)], covalently linked to a heterotypic T-cell epitope from either non-structural protein 3A [3A (21–35)] or 3D [3D (56–70)], named B2T-3A and B2T-3D, respectively, elicit high levels of neutralizing antibodies (nAbs) and IFN-γ-producing cells in pigs. To assess whether the inclusion and orientation of T-3A and T-3D T-cell epitopes in a single molecule could modulate immunogenicity, dendrimers with T epitopes juxtaposed in both possible orientations, i.e., constructs B2TT-3A3D and B2TT-3D3A, were made and tested in pigs. Both dendrimers elicited high nAbs titers that broadly neutralized type O FMDVs, although B2TT-3D3A did not respond to boosting, and induced lower IgGs titers, in particular IgG2, than B2TT-3A3D. Pigs immunized with B2, a control dendrimer displaying two B-cell epitope copies and no T-cell epitope, gave no nABs, confirming T-3A and T-3D as T helper epitopes. The T-3D peptide was found to be an immunodominant, as it produced more IFN-γ expressing cells than T-3A in the in vitro recall assay. Besides, in pigs immunized with the different dendrimeric peptides, CD4+ T-cells were the major subset contributing to IFN-γ expression upon in vitro recall, and depletion of CD4+ cells from PBMCs abolished the production of this cytokine. Most CD4+IFN-γ+ cells showed a memory (CD4+2E3−) and a multifunctional phenotype, as they expressed both IFN-γ and TNF-α, suggesting that the peptides induced a potent Th1 pro-inflammatory response. Furthermore, not only the presence, but also the orientation of T-cell epitopes influenced the T-cell response, as B2TT-3D3A and B2 groups had fewer cells expressing both cytokines. These results help understand how B2T-type dendrimers triggers T-cell populations, highlighting their potential as next-generation FMD vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2020.621537/fullfoot-and-mouth disease virusvaccinesdendrimer peptideT cell phenotypecytokine |
| spellingShingle | Patricia de León Rodrigo Cañas-Arranz Sira Defaus Elisa Torres Mar Forner María J. Bustos Concepción Revilla Javier Dominguez David Andreu Esther Blanco Francisco Sobrino Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes Frontiers in Immunology foot-and-mouth disease virus vaccines dendrimer peptide T cell phenotype cytokine |
| title | Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes |
| title_full | Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes |
| title_fullStr | Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes |
| title_full_unstemmed | Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes |
| title_short | Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes |
| title_sort | swine t cells and specific antibodies evoked by peptide dendrimers displaying different fmdv t cell epitopes |
| topic | foot-and-mouth disease virus vaccines dendrimer peptide T cell phenotype cytokine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.621537/full |
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