title: Intranasal immunization of baculovirus displayed hemagglutinin confers complete protection against mouse adapted highly pathogenic H7N7 reassortant influenza virus.
abstract: BACKGROUND
  Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus.
  
  
  RESULTS
  In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA). The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n.) or subcutaneously (s.c.) with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs.
  
  
  CONCLUSIONS
  Our results indicated that protection from high pathogenic H7N7 (NL/219/03) virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections.
authors.affiliation: Animal Health Biotechnology, Temasek Lifesciences Laboratory, National University of Singapore, Singapore, Singapore.
authors.forename: Subaschandrabose
authors.initials: S
authors.lastname: Rajesh Kumar
authors.forename: Syed Musthaq
authors.initials: SM
authors.lastname: Syed Khader
authors.forename: Tanja K
authors.initials: TK
authors.lastname: Kiener
authors.forename: Milene
authors.initials: M
authors.lastname: Szyporta
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kwang
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007114:Immunization; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology*; D015203:Reproducibility of Results; D040521:Subcutaneous Tissue / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines