title: Identification and characterisation of T-cell epitopes for incorporation into dendritic cell-delivered Listeria vaccines.
abstract: Dendritic cells loaded with antigenic peptides, because of their safety and robust immune stimulation, would be ideal for induction of immunity to protect against listeriosis. However, there is no currently accepted method to predict which peptides derived from the Listeria proteome might confer protection. While elution of peptides from MHC molecules after Listeria infection yields high-affinity immune-dominant epitopes, these individual epitopes did not reliably confer Listeria protection. Instead we applied bioinformatic predictions of MHC class I and II epitopes to generate antigenic peptides that were then formulated with Advax™, a novel polysaccharide particulate adjuvant able to enhance cross-presentation prior to being screened for their ability to induce protective T-cell responses. A combination of at least four intermediate strength MHC-I binding epitopes and one weak MHC-II binding epitope when expressed in a single peptide sequence and formulated with Advax adjuvant induced a potent T-cell response and high TNF-α and IL-12 production by dendritic cells resulting in robust listeriosis protection in susceptible mice. This T-cell vaccine approach might be useful for the design of vaccines to protect against listeriosis or other intracellular infections.
authors.affiliation: Grupo de Genómica, Proteómica y Vacunas, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Calderon-Gonzalez
authors.affiliation: Information Technologies Research Group, Era7 Bioinformatics, Granada, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Tobes
authors.affiliation: Information Technologies Research Group, Era7 Bioinformatics, Granada, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pareja
authors.affiliation: Grupo de Genómica, Proteómica y Vacunas, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Frande-Cabanes
authors.affiliation: Department of Diabetes and Endocrinology, Flinders University, Adelaide, Australia; Vaxine Pty Ltd, Flinders Medical Center, Adelaide, Australia.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Grupo de Genómica, Proteómica y Vacunas, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain. Electronic address: calvarez@humv.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Dominguez
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology*; D019295:Computational Biology / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000737:chemistry / Q000276:immunology; D008087:Listeria / Q000276:immunology*; D008088:Listeriosis / Q000517:prevention & control*; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D015203:Reproducibility of Results; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
keywords: Dendritic cells; Glyceraldehyde-3-phosfate-dehydrogenase; Listeriolysin O; Listeriosis; Vaccines