title: Oral Delivery of a Novel Attenuated Salmonella Vaccine Expressing Influenza A Virus Proteins Protects Mice against H5N1 and H1N1 Viral Infection.
abstract: Attenuated strains of invasive enteric bacteria, such as Salmonella, represent promising gene delivery agents for nucleic acid-based vaccines as they can be administrated orally. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the hemagglutinin (HA) and neuraminidase (NA) of a highly pathogenic H5N1 influenza virus. We showed that the constructed Salmonella strain exhibited efficient gene transfer activity for HA and NA expression and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we evaluated the immune responses and protection induced by the constructed Salmonella-based vaccine. Our study showed that the Salmonella-based vaccine induced significant production of anti-HA serum IgG and mucosal IgA, and of anti-HA interferon-γ producing T cells in orally vaccinated mice. Furthermore, mice orally vaccinated with the Salmonella vaccine expressing viral HA and NA proteins were completely protected from lethal challenge of highly pathogenic H5N1 as well as H1N1 influenza viruses while none of the animals treated with the Salmonella vaccine carrying the empty expression vector with no viral antigen expression was protected. These results suggest that the Salmonella-based vaccine elicits strong antigen-specific humoral and cellular immune responses and provides effective immune protection against multiple strains of influenza viruses. Furthermore, our study demonstrates the feasibility of developing novel attenuated Salmonella strains as new oral vaccine vectors against influenza viruses.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Zenglin
authors.initials: Z
authors.lastname: Pei
authors.affiliation: School of Public Health, University of California, Berkeley, California, United States of America.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Taizhou Institute of Virology, Taizhou, Jiangsu, China; Jiangsu Affynigen Biotechnologies, Inc., Taizhou, Jiangsu, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Ren
authors.affiliation: School of Public Health, University of California, Berkeley, California, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Gong
authors.affiliation: Program in Comparative Biochemistry, University of California, Berkeley, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Reeves
authors.affiliation: Program in Comparative Biochemistry, University of California, Berkeley, California, United States of America.
authors.forename: Jingxue
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Taizhou Institute of Virology, Taizhou, Jiangsu, China; Jiangsu Affynigen Biotechnologies, Inc., Taizhou, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Zishu
authors.initials: Z
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China; School of Public Health, University of California, Berkeley, California, United States of America; Program in Comparative Biochemistry, University of California, Berkeley, California, United States of America.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Public Health, University of California, Berkeley, California, United States of America; Program in Comparative Biochemistry, University of California, Berkeley, California, United States of America.
authors.forename: Sangwei
authors.initials: S
authors.lastname: Lu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D006388:Hemagglutinins; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D009439:Neuraminidase