title: Mucosal immunization with attenuated Shigella flexneri harboring an influenza hemagglutinin DNA vaccine protects mice against a lethal influenza challenge.
abstract: Mucosal surfaces are important for the induction of immunity against influenza virus. In a murine intranasal immunization model, we demonstrated that the attenuated Shigella flexneri Deltaasd strain 15D, carrying a DNA construct encoding the influenza virus hemagglutinin (HA), induces protective immunity against a lethal respiratory challenge with influenza A/WSN/33. Influenza virus-specific IFN-gamma T cells were detected among splenocytes, and anti-HA IgG was detected in serum post-immunization, albeit at low levels. Following influenza virus challenge, an accelerated anti-HA IgA antibody response was detected in bronchoalveolar lavage (BAL) washings from mice vaccinated with attenuated shigella containing the HA construct. These results suggest that S. flexneri Deltaasd strain 15D is a promising vector for mucosal DNA vaccine immunization against influenza virus and other mucosal pathogens.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Vecino
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Quanquin
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Sobrido
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Sesma
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Fennelly
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001483:Base Sequence; D005260:Female; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D010957:Plasmids / Q000235:genetics; D012763:Shigella flexneri / Q000235:genetics* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA