title: Baculovirus Displaying Hemagglutinin Elicits Broad Cross-Protection against Influenza in Mice.
abstract: The widespread influenza virus infection further emphasizes the need for novel vaccine strategies that effectively reduce the impact of epidemic as well as pandemic influenza. Conventional influenza vaccines generally induce virus neutralizing antibody responses which are specific for a few antigenically related strains within the same subtype. However, antibodies directed against the conserved stalk domain of HA could neutralize multiple subtypes of influenza virus and thus provide broad-spectrum protection. In this study, we designed and constructed a recombinant baculovirus-based vaccine, rBac-HA virus, that expresses full-length HA of pandemic H1N1 influenza virus (A/California/04/09) on the viral envelope. We demonstrated that repeated intranasal immunizations with rBac-HA virus induced HA stalk-specific antibody responses and protective immunity against homologous as well as heterosubtypic virus challenge. The adoptive transfer experiment shows that the cross-protection is conferred by the immune sera which contain HA stalk-specific antibodies. These results warrant further development of rBac-HA virus as a broad-protective vaccine against influenza. The vaccine induced protection against infection with the same subtype as well as different subtype, promising a potential universal vaccine for broad protection against different subtypes to control influenza outbreaks including pandemic.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Sim
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Baik Lin
authors.initials: BL
authors.lastname: Seong
authors.affiliation: Laboratory of Viral Immunology, International Vaccine Institute, Seoul, Korea.
authors.forename: Huan Huu
authors.initials: HH
authors.lastname: Nguyen
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
mesh_terms: D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D016367:Baculoviridae / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D056738:Cross Protection / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D056724:Immunity, Humoral; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology*; D011995:Recombination, Genetic / Q000235:genetics; D013154:Spleen / Q000473:pathology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007106:Immune Sera