title: Mucosal immune features to phosphorylcholine by nasal Flt3 ligand cDNA-based vaccination.
abstract: Phosphorylcholine (PC) is an immunodominant epitope in some pathogens including Streptococcus pneumoniae and it is well-known that PC-specific antibodies (Abs) play a key role in the induction of protective immunity against pneumococcal infection. In this study, we examined whether nasal administration of DNA plasmid encoding Flt3 ligand gene (pFL) as a mucosal adjuvant plus PC-conjugated keyhole limpet hemocyanin (PC-KLH), would elicit PC-specific immune responses, and characterized mucosal immune responses to PC induced by this nasal vaccination. Nasal immunization with pFL plus PC-KLH enhanced induction of PC-specific IgA and IgM Abs in airway secretions when compared with mice given PC-KLH with or without empty plasmid gene (pORF) as controls; in addition to the mucosal immune responses, PC-specific immune responses in serum were also induced. Furthermore, the mucosal and serum IgA and IgM Abs in mice given pFL plus PC-KLH nasally, exhibited high-specificity for the PC molecule. Of interest, the PC-specific Abs bound dose-dependently to anti-T15 idiotype (AB1-2). Thus, the inhibition of S. pneumoniae colonization on the nasal cavity and lungs after nasal challenge with the live organism was significantly elicited in mice immunized with pFL plus PC-KLH compared to that of mice immunized with antigen with pORF. Taken together, these findings show that nasal administration of pFL with PC-KLH elicited T15-like anti-PC IgA and IgM Abs in the respiratory tracts, and further attenuated S. pneumoniae colonization on the respiratory tracts. Nasal administration of Flt3 ligand cDNA with PC may contribute to the development of nasal vaccination for prevention of S. pneumoniae infection.
authors.affiliation: Department of Preventive Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: Tselmeg
authors.initials: T
authors.lastname: Baatarjav
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kataoka
authors.forename: Rebekah S
authors.initials: RS
authors.lastname: Gilbert
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terao
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukui
authors.forename: Masaki
authors.initials: M
authors.lastname: Goto
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kawabata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Hiro-O
authors.initials: HO
authors.lastname: Ito
mesh_terms: D000281:Administration, Intranasal; D058956:Administration, Mucosal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018076:DNA, Complementary / Q000276:immunology; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010767:Phosphorylcholine / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018076:DNA, Complementary; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D008565:Membrane Proteins; D019444:Vaccines, DNA; C084881:flt3 ligand protein; D010767:Phosphorylcholine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin