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Title:   Author  item
                                            GUTIERREZ, ANDRES - University Of Rhode Islanditem
                                            Loving, Crystalitem
                                            MOISE, LEONARD - University Of Rhode Islanditem
                                            TERRY, FRANCES - Epivax, Incitem
                                            Brockmeier, Susanitem
                                            Hughes, Hollyitem
                                            MARTIN, WILLIAM - Epivax, Incitem
                                            DE GROOT, ANNE - University Of Rhode Island
  Submitted to: PLOS ONE
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/5/2016
                                    Publication  Date: 7/13/2016
                                    Citation: Gutierrez, A.H., Loving, C., Moise, L., Terry, F.E., Brockmeier, S.L., Hughes, H.R., Martin, W.D., De Groot, A.S. 2016. In vivo validation of predicted and conserved T cell epitopes in a swine influenza model. PLoS One. 11(7):e0159237.Interpretive Summary: Swine influenza is a problem for swine producers because of the large number of different strains currently present in the U.S. swine population. While some portions of the virus are different, there are some portions that are the same across a number of different strains. A newer vaccine that includes portions of the virus that a specific immune cell recognizes could provide a baseline level of protection against numerous strains of influenza. Vaccines for prevention of infection and disease currently available do not provide the best protection; thus, it is necessary to explore new vaccines for limiting the economic impact of influenza in pigs. Our work shows that the bioinformatics tools available to identify conserved portions of the virus as it relates to the swine immune system are functional and the information gained from our analysis is important for future vaccine design. Consideration should be given for the type of vaccine used that includes the identified portions of viruses that the immune system recognizes. Collectively, the information reported is important for generation of swine influenza virus vaccines, as well as vaccines for other diseases of swine.
                                Technical 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 using inactivated whole-virus, subunit and alpha replicon-based vaccines do not provide broad protection against the diverse strains of IAV currently circulating in US swine. Here, we used immunoinformatic tools to construct and test an epitope-driven IAV vaccine. We identified class I and II T cell epitopes conserved in seven representative strains of IAV in US swine and predicted to bind to SLA alleles reported as prevalent in commercial swine. Pigs were immunized with two multi-epitope plasmid DNA vaccines encoding strings of class I and II epitopes. Prior to H1N1 challenge of the immunized pigs, epitope-specific interferon-gamma (IFN-gamma) recall responses were detected, confirming the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrating its potential for use in the design of vaccines for swine.


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