Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic
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Administration, Intranasal
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Animals
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Antibodies, Viral / analysis*
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Antibodies, Viral / blood
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Chitin / immunology
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Cholera Toxin / immunology
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Disease Models, Animal
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Female
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology*
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Immunity, Mucosal
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Immunoglobulin A / analysis
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Immunoglobulin G / blood
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Influenza A Virus, H5N1 Subtype / immunology*
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Influenza Vaccines / administration & dosage
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Influenza Vaccines / immunology*
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Lymphoid Tissue / immunology
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Mice
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Mice, Inbred BALB C
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Microspheres
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Nasal Mucosa / immunology
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Orthomyxoviridae Infections / prevention & control*
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Orthomyxoviridae Infections / virology
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Poly I-C / immunology
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RNA, Double-Stranded / immunology
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Spleen / immunology
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Toll-Like Receptors / biosynthesis
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Vaccines, Subunit / genetics
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Vaccines, Subunit / immunology
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Viral
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Hemagglutinin Glycoproteins, Influenza Virus
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Immunoglobulin A
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Immunoglobulin G
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Influenza Vaccines
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RNA, Double-Stranded
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Toll-Like Receptors
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Vaccines, Subunit
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Vaccines, Synthetic
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hemagglutinin, human influenza A virus
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Chitin
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Cholera Toxin
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Poly I-C