title: Type IVB pilus operon promoter controlling expression of the severe acute respiratory syndrome-associated coronavirus nucleocapsid gene in Salmonella enterica Serovar Typhi elicits full immune response by intranasal vaccination.
abstract: Attenuated Salmonella enterica serovar Typhi strains have been considered to be attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar Typhi strain stably expressing conserved nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) by integrating the N gene into the pilV gene, which was under the control of the type IVB pilus operon promoter in S. enterica serovar Typhi. BALB/c mice were immunized with this recombinant strain through different routes: intranasally, orogastrically, intraperitoneally, and intravenously. Results showed that the intranasal route caused the highest production of specific immunoglobulin G (IgG), IgG2a, and secretory IgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T-lymphocyte activities and increased gamma interferon-producing T cells compared with the parental strain. Our work provides insights into how the type IVB pilus operon promoter controlling SARS-CoV N gene expression in Salmonella might be attractive for a live-vector vaccine against SRAS-CoV infection, for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pilus operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.
authors.affiliation: Department of Immunology, Hubei Province Key Laboratory of Allergy and Immune-Related Diseases, The State Key Laboratory of Virology, Wuhan University School of Medicine, Wuhan 430071, People's Republic of China.
authors.forename: Fengling
authors.initials: F
authors.lastname: Luo
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Pingfei
authors.initials: P
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.forename: Victor Tunje
authors.initials: VT
authors.lastname: Jeza
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000086462:Coronavirus Nucleocapsid Proteins; D005260:Female; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D006801:Humans; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009876:Operon; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000276:immunology*; D012485:Salmonella typhi / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D001426:Bacterial Proteins; D000086462:Coronavirus Nucleocapsid Proteins; D019590:Nucleocapsid Proteins; C077573:PilV protein, Bacteria; D014765:Viral Vaccines