PMID- 26909080 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160224 LR - 20181113 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 7 DP - 2016 TI - The Non-structural Protein 5 and Matrix Protein Are Antigenic Targets of T Cell Immunity to Genotype 1 Porcine Reproductive and Respiratory Syndrome Viruses. PG - 40 LID - 10.3389/fimmu.2016.00040 [doi] LID - 40 AB - The porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focused on envelope glycoproteins to target virus-neutralizing antibody responses. However, these approaches have failed to demonstrate the necessary efficacy to progress toward market. T cells are crucial to the control of many viruses through cytolysis and cytokine secretion. Since control of PRRSV infection is not dependent on the development of neutralizing antibodies, it has been proposed that T cell-mediated immunity plays a key role. Therefore, we hypothesized that conserved T cell antigens represent prime candidates for the development a novel PRRS vaccine. Antigens were identified by screening a proteome-wide synthetic peptide library with T cells from cohorts of pigs rendered immune by experimental infections with a closely related (subtype 1) or divergent (subtype 3) PRRSV-1 strain. Dominant T cell IFN-gamma responses were directed against the non-structural protein 5 (NSP5), and to a lesser extent, the matrix (M) protein. The majority of NSP5-specific CD8 T cells and M-specific CD4 T cells expressed a putative effector memory phenotype and were polyfunctional as assessed by coexpression of TNF-alpha and mobilization of the cytotoxic degranulation marker CD107a. Both antigens were generally well conserved among strains of both PRRSV genotypes. Thus, M and NSP5 represent attractive vaccine candidate T cell antigens, which should be evaluated further in the context of PRRSV vaccine development. FAU - Mokhtar, Helen AU - Mokhtar H AD - Virology Department, Animal and Plant Health Agency, Addlestone, UK; Department of Microbial and Cellular Sciences, University of Surrey, Guildford, UK. FAU - Pedrera, Miriam AU - Pedrera M AD - Virology Department, Animal and Plant Health Agency , Addlestone , UK. FAU - Frossard, Jean-Pierre AU - Frossard JP AD - Virology Department, Animal and Plant Health Agency , Addlestone , UK. FAU - Biffar, Lucia AU - Biffar L AD - Virology Department, Animal and Plant Health Agency , Addlestone , UK. FAU - Hammer, Sabine E AU - Hammer SE AD - Department of Pathobiology, Institute of Immunology, University of Veterinary Medicine Vienna , Vienna , Austria. FAU - Kvisgaard, Lise K AU - Kvisgaard LK AD - National Veterinary Institute, Technical University of Denmark , Frederiksberg , Denmark. FAU - Larsen, Lars E AU - Larsen LE AD - National Veterinary Institute, Technical University of Denmark , Frederiksberg , Denmark. FAU - Stewart, Graham R AU - Stewart GR AD - Department of Microbial and Cellular Sciences, University of Surrey , Guildford , UK. FAU - Somavarapu, Satyanarayana AU - Somavarapu S AD - School of Pharmacy, University College London , London , UK. FAU - Steinbach, Falko AU - Steinbach F AD - Virology Department, Animal and Plant Health Agency , Addlestone , UK. FAU - Graham, Simon P AU - Graham SP AD - Virology Department, Animal and Plant Health Agency , Addlestone , UK. LA - eng PT - Journal Article DEP - 20160216 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC4755262 OTO - NOTNLM OT - IFN-gamma OT - T cell OT - antigen identification OT - phenotype and function OT - porcine reproductive and respiratory syndrome virus OT - vaccine EDAT- 2016/02/26 06:00 MHDA- 2016/02/26 06:01 PMCR- 2016/01/01 CRDT- 2016/02/25 06:00 PHST- 2015/10/29 00:00 [received] PHST- 2016/01/26 00:00 [accepted] PHST- 2016/02/25 06:00 [entrez] PHST- 2016/02/26 06:00 [pubmed] PHST- 2016/02/26 06:01 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2016.00040 [doi] PST - epublish SO - Front Immunol. 2016 Feb 16;7:40. doi: 10.3389/fimmu.2016.00040. eCollection 2016.