title: Intranasal immunization with recombinant HA and mast cell activator C48/80 elicits protective immunity against 2009 pandemic H1N1 influenza in mice.
abstract: BACKGROUND
  Pandemic influenza represents a major threat to global health. Vaccination is the most economic and effective strategy to control influenza pandemic. Conventional vaccine approach, despite being effective, has a number of major deficiencies including limited range of protection, total dependence on embryonated eggs for production, and time consuming for vaccine production. There is an urgent need to develop novel vaccine strategies to overcome these deficiencies.
  
  
  RESULTS
  The major objective of this work was to develop a novel vaccine strategy combining recombinant haemagglutinin (HA) protein and a master cell (MC) activator C48/80 for intranasal immunization. We demonstrated in BALB/c mice that MC activator C48/80 had strong adjuvant activity when co-administered with recombinant HA protein intranasally. Vaccination with C48/80 significantly increased the serum IgG and mucosal surface IgA antibody responses against HA protein. Such increases correlated with stronger and durable neutralizing antibody activities, offering protection to vaccinated animals from disease progression after challenge with lethal dose of A/California/04/2009 live virus. Furthermore, protected animals demonstrated significant reduction in lung virus titers, minimal structural alteration in lung tissues as well as higher and balanced production of Th1 and Th2 cytokines in the stimulated splenocytes when compared to those without C48/80.
  
  
  CONCLUSIONS
  The present study demonstrates that the novel vaccine approach of combining recombinant HA and mucosal adjuvant C48/80 is safe and effective in eliciting protective immunity in mice. Future studies on the mechanism of action of C48/80 and potential combination with other vaccine strategies such as prime and boost approach may help to induce even more potent and broad immune responses against viruses from various clades.
authors.affiliation: AIDS Research Center, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Meng
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Mei
authors.forename: Linlin
authors.initials: L
authors.lastname: Bao
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.forename: Rongyue
authors.initials: R
authors.lastname: Lei
authors.forename: Liangzhi
authors.initials: L
authors.lastname: Xie
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006388:Hemagglutinins / Q000276:immunology*; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000627:therapeutic use*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D058873:Pandemics; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000276:immunology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D006388:Hemagglutinins; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D003189:p-Methoxy-N-methylphenethylamine