title: A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging.
abstract: Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)(3) as a dendritic cell (DC)-targeting double mucosal adjuvant elicited ovalbumin-specific secretory IgA (S-IgA) antibody (Ab) responses, we examined whether this double adjuvant could induce influenza-specific protective immunity in aged mice. A double adjuvant plus A/Puerto Rico/8/34 (PR8) hemagglutinin (HA) induced increased numbers of CD11b(+) CD11c(+) DCs and both CD4(+) Th1- and Th2-type responses in the nasopharyngeal-associated lymphoreticular tissue, nasal passages and cervical lymph nodes. Further, increased levels of PR8 HA-specific S-IgA Ab responses were detected in the upper respiratory tact (URT) of aged and young adult mice given nasal PR8 HA with this double adjuvant. Thus, when mice were challenged with PR8 virus via the nasal route, both aged and young adult mice given nasal vaccine exhibited complete protection. Further, IgA-deficient mice nasally immunized with a double adjuvant influenza vaccine failed to provide protection against PR8 challenge. These results indicate that a nasal double adjuvant successfully induces PR8 HA-specific IgA Ab responses in both young adult and aged mice, which are essential for the prevention of influenza infection in the murine URT.
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Asanuma
authors.forename: Normaiza Binti
authors.initials: NB
authors.lastname: Zamri
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sekine
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fukuyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tokuhara
authors.forename: Rebekah S
authors.initials: RS
authors.lastname: Gilbert
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fukuiwa
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008565:Membrane Proteins / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C084881:flt3 ligand protein
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