Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection

Microbes Infect. 2006 Oct;8(12-13):2706-14. doi: 10.1016/j.micinf.2006.07.018. Epub 2006 Aug 28.


Attenuated recombinant H5N1 influenza virus was constructed to develop a safe H5N1 influenza vaccine. The immunogenicity and protective effect of the vaccine prepared from haemagglutinin-modified recombinant H5N1 influenza virus was evaluated in mice intranasally co-administered with cholera toxin B subunit containing a trace amount of holotoxin (CTB*), synthetic double-stranded RNA, poly (I:C) or chitin microparticles (CMP) as adjuvants. Intranasal administration of recombinant H5 HA split vaccine with CTB* or poly(I:C) and/or CMP elicited an immunological response with both anti-H5 HA IgA in the nasal wash and anti-H5 HA IgG antibody in the serum, and showed a protective against lethal H5N1 A/Hong Kong/483/97 (HK483) infection. We also demonstrated that intranasal co-administration of antigen with both poly (I:C) and CMP enhanced the expression of Toll-like receptor (TLR) 3, TLR7 in the spleen. These results indicate that poly (I:C) and CMP are highly effective as mucosal adjuvants for use with the nasal H5N1 vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / analysis*
  • Antibodies, Viral / blood
  • Chitin / immunology
  • Cholera Toxin / immunology
  • Disease Models, Animal
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Immunity, Mucosal
  • Immunoglobulin A / analysis
  • Immunoglobulin G / blood
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Inbred BALB C
  • Microspheres
  • Nasal Mucosa / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Orthomyxoviridae Infections / virology
  • Poly I-C / immunology
  • RNA, Double-Stranded / immunology
  • Spleen / immunology
  • Toll-Like Receptors / biosynthesis
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin A
  • Immunoglobulin G
  • Influenza Vaccines
  • RNA, Double-Stranded
  • Toll-Like Receptors
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • hemagglutinin, human influenza A virus
  • Chitin
  • Cholera Toxin
  • Poly I-C