title: Influenza A virus nucleoprotein derived from Escherichia coli or recombinant vaccinia (Tiantan) virus elicits robust cross-protection in mice.
abstract: BACKGROUND
  Immunity to conserved viral antigens is an attractive approach to develop a universal vaccine against epidemic and pandemic influenza. A nucleoprotein (NP)-based vaccine has been explored and preliminary studies have shown promise. However, no study has explored the immunity and cross-protective efficacy of recombinant NP derived from Escherichia coli compared with recombinant vaccinia virus (Tiantan).
  
  
  METHODS
  Recombinant NP protein (rNP) from influenza virus A/Jingke/30/95(H3N2) was obtained from E. coli and recombinant vaccinia virus (Tiantan) RVJ1175NP. Purified rNP without adjuvant and RVJ1175NP were used to immunize BALB/c mice intramuscularly. Humoral immune responses were detected by ELISA, while cell-mediated immune responses were measured by ex vivo IFN-γ ELISPOT and in vivo cytotoxicity assays. The cross-protective efficacy was assessed by a challenge with a heterosubtype of influenza virus A/PR/8/34(H1N1).
  
  
  RESULTS
  Our results demonstrate that a high dose (90 μg) of rNP induced NP-specific antibodies and T cell responses that were comparable with those of RVJ1175NP in mice. Importantly, the survival ratio (36, 73, and 78%) of the vaccinated mice after the influenza virus A/PR/8/34(H1N1) challenge was rNP vaccine dose-dependent (10, 30, and 90 μg, respectively), and no significant differences were observed between the rNP- and RVJ1175NP-immunized (91%) mice.
  
  
  CONCLUSIONS
  Influenza A virus NP derived from E. coli or recombinant vaccinia (Tiantan) virus elicited cross-protection against influenza virus in mice, and the immune response and protective efficacy of rNP were comparable to RVJ1175NP. These data provide a basis for the use of prokaryotically expressed NP as a candidate universal influenza vaccine.
authors.affiliation: Biotech Center for Viral Disease Emergency, National Institute for Viral Disease Control and Prevention (IVDC), Chinese Center for Disease Control and Prevention (CCDC), Changbai Road 155, Changping District, Beijing, 102206, People's Republic of China.
authors.forename: Baoying
authors.initials: B
authors.lastname: Huang
authors.forename: Wenling
authors.initials: W
authors.lastname: Wang
authors.forename: Renqing
authors.initials: R
authors.lastname: Li
authors.forename: Xiuping
authors.initials: X
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Qi
authors.forename: Yingying
authors.initials: Y
authors.lastname: Gao
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
authors.forename: Li
authors.initials: L
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D056738:Cross Protection; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007111:Immunity, Cellular; D007115:Immunization Schedule; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016019:Survival Analysis; D014170:Transformation, Genetic; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins