In Vivo Validation of Predicted and Conserved T Cell Epitopes in a Swine Influenza Model
Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As...
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| Vydáno v: | PloS one Ročník 11; číslo 7; s. e0159237 |
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| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
Public Library of Science
13.07.2016
Public Library of Science (PLoS) |
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| ISSN: | 1932-6203, 1932-6203 |
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| Abstract | Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFNγ) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi-epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFNγ responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs. |
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| AbstractList | Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFNγ) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi-epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFNγ responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs. Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFNγ) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi-epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFNγ responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs.Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFNγ) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi-epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFNγ responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs. Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFN[gamma]) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi-epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFN[gamma] responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs. |
| Audience | Academic |
| Author | Loving, Crystal De Groot, Anne S. Gutiérrez, Andres H. Brockmeier, Susan L. Martin, William D. Hughes, Holly R. Moise, Leonard Terry, Frances E. |
| AuthorAffiliation | 1 Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI, United States of America 2 Virus and Prion Diseases Research Unit, NADC, USDA ARS, Ames, IA, United States of America 3 EpiVax Inc., Providence, RI, United States of America Icahn School of Medicine at Mount Sinai, UNITED STATES |
| AuthorAffiliation_xml | – name: 2 Virus and Prion Diseases Research Unit, NADC, USDA ARS, Ames, IA, United States of America – name: Icahn School of Medicine at Mount Sinai, UNITED STATES – name: 1 Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI, United States of America – name: 3 EpiVax Inc., Providence, RI, United States of America |
| Author_xml | – sequence: 1 givenname: Andres H. surname: Gutiérrez fullname: Gutiérrez, Andres H. – sequence: 2 givenname: Crystal surname: Loving fullname: Loving, Crystal – sequence: 3 givenname: Leonard surname: Moise fullname: Moise, Leonard – sequence: 4 givenname: Frances E. surname: Terry fullname: Terry, Frances E. – sequence: 5 givenname: Susan L. surname: Brockmeier fullname: Brockmeier, Susan L. – sequence: 6 givenname: Holly R. surname: Hughes fullname: Hughes, Holly R. – sequence: 7 givenname: William D. surname: Martin fullname: Martin, William D. – sequence: 8 givenname: Anne S. surname: De Groot fullname: De Groot, Anne S. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27411061$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Competing Interests: ADG and WDM are senior officers and majority shareholders at EpiVax, Inc., a privately-owned immunoinformatics and vaccine design company located in Providence, RI, USA. LM and FET are employees at EpiVax, in which LM holds stock options. ADG, WDM, LM and FET acknowledge that there is a potential conflict of interest related to their relationship with EpiVax and attest that the work contained in this research report is free of any bias that might be associated with the commercial goals of the company. This study was conducted in part with funding from National Pork Board. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare. Conceived and designed the experiments: AHG CL LM ADG WDM. Performed the experiments: AHG CL SLB HRH. Analyzed the data: AHG CL LM ADG FET. Contributed reagents/materials/analysis tools: AHG CL WDM ADG. Wrote the paper: AHG CL LM ADG WDM FET SLB HRH. |
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| SubjectTerms | Agricultural economics Alleles Analysis Animals Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Biology and Life Sciences Computational Biology - methods Deoxyribonucleic acid DNA DNA vaccines Dosage and administration Epitopes Epitopes, T-Lymphocyte - immunology Haplotypes Histocompatibility Antigens Class II - immunology Hogs Immune response Immunization Immunogenicity Infections Influenza Influenza A Influenza A virus Influenza A virus - genetics Influenza A virus - immunology Influenza Vaccines - immunology Interferon Interferon-gamma - immunology Leukocytes Livestock Lymphocytes T Medicine and health sciences Orthomyxoviridae Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - prevention & control Orthomyxoviridae Infections - virology Peptides Performance prediction Physiological aspects Plasmids Research and Analysis Methods Retrospective Studies Risk factors Strains (organisms) Strings Swine Swine Diseases - immunology Swine Diseases - virology Swine flu Swine influenza T cell receptors T cells Vaccines Vaccines, DNA - immunology Viruses γ-Interferon |
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| Title | In Vivo Validation of Predicted and Conserved T Cell Epitopes in a Swine Influenza Model |
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| Volume | 11 |
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