title: Intranasal hydroxypropyl-β-cyclodextrin-adjuvanted influenza vaccine protects against sub-heterologous virus infection.
abstract: Intranasal vaccination with inactivated influenza viral antigens is an attractive and valid alternative to currently available influenza (flu) vaccines; many of which seem to need efficient and safe adjuvant, however. In this study, we examined whether hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used pharmaceutical excipient to improve solubility and drug delivery, can act as a mucosal adjuvant for intranasal flu vaccines. We found that intranasal immunization of mice with hemagglutinin split- as well as inactivated whole-virion influenza vaccine with HP-β-CD resulted in secretion of antigen-specific IgA and IgGs in the airway mucosa and the serum as well. As a result, both HP-β-CD adjuvanted-flu intranasal vaccine protected mice against lethal challenge with influenza virus, equivalent to those induced by experimental cholera toxin-adjuvanted ones. Of note, intranasal use of HP-β-CD as an adjuvant induced significantly lower antigen-specific IgE responses than that induced by aluminum salt adjuvant. These results suggest that HP-β-CD may be a potent mucosal adjuvant for seasonal and pandemic influenza vaccine.
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Kusakabe
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ozasa
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kobari
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Momota
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kishishita
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobiyama
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, Japan.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, Japan. Electronic address: kenishii@biken.osaka-u.ac.jp.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016503:Drug Delivery Systems; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D018928:Immunity, Mucosal; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: Adjuvant; Cyclodextrin; Damage-associated molecular patterns; Excipient; Influenza; Intranasal immunization