title: Efficient induction of cytotoxic T lymphocytes specific for severe acute respiratory syndrome (SARS)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a.
abstract: Spike and nucleocapsid are structural proteins of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and major targets for cytotoxic T lymphocytes (CTLs). In contrast, non-structural proteins encoded by two-thirds of viral genome are poorly characterized for cell-mediated immunity. We previously demonstrated that nucleocapsid-derived peptides chemically coupled to the surface of liposomes effectively elicited SARS-CoV-specific CTLs in mice. Here, we attempted to identify HLA-A*0201-restricted CTL epitopes derived from a non-structural polyprotein 1a (pp1a) of SARS-CoV, and investigated whether liposomal peptides derived from pp1a were effective for CTL induction. Out of 30 peptides predicted on computational algorithms, nine peptides could significantly induce interferon gamma (IFN-gamma)-producing CD8(+) T cells in mice. These peptides were coupled to the surface of liposomes, and inoculated into mice. Six liposomal peptides effectively induced IFN-gamma-producing CD8(+) T cells and seven liposomal peptides including the six peptides primed CTLs showing in vivo killing activities. Further, CTLs induced by the seven liposomal peptides lysed an HLA-A*0201 positive cell line expressing naturally processed, pp1a-derived peptides. Of note, one of the liposomal peptides induced high numbers of long-lasting memory CTLs. These data suggest that surface-linked liposomal peptides derived from pp1a might offer an efficient CTL-based vaccine against SARS.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kohyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohno
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suda
authors.forename: Maiko
authors.initials: M
authors.lastname: Taneichi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Masahito
authors.initials: M
authors.lastname: Mori
authors.forename: Akiharu
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Hayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Uchida
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D006801:Humans; D007114:Immunization; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000276:immunology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines
chemical_list: D018984:Epitopes, T-Lymphocyte; D008081:Liposomes; D010455:Peptides; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; C521592:Nsp1 protein, SARS coronavirus; D012324:RNA-Dependent RNA Polymerase