A combination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity.
We explore cellular and molecular mechanisms of nasal adjuvant of a combination of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligodeoxynucleotides (CpG ODN). The double DNA adjuvant given with OVA maintained prolonged OVA-specific secretory IgA (S-IgA) Ab responses in external secretions for more than 25 weeks after the final immunization. Further, both Th1- and Th2-type cytokine responses were induced by this combined adjuvant regimen. The frequencies of plasmacytoid DCs (pDCs) and CD8(+) DCs were significantly increased in nasopharyngeal-associated lymphoreticular tissue (NALT) of mice given the combined adjuvant. Importantly, when we examined adjuvanticity of pFL plus CpG ODN in 2-year-old mice, significant levels of mucosal IgA Ab responses were also induced. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for the development of an effective mucosal vaccine for the elderly.
Fukuiwa
Tatsuya
T
The Immunobiology Vaccine Center, Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
Sekine
Shinichi
S
Kobayashi
Ryoki
R
Suzuki
Hideaki
H
Kataoka
Kosuke
K
Gilbert
Rebekah S
RS
Kurono
Yuichi
Y
Boyaka
Prosper N
PN
Krieg
Arthur M
AM
McGhee
Jerry R
JR
Fujihashi
Kohtaro
K
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology*; D009305:Nasopharynx / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D010957:Plasmids / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D018076:DNA, Complementary; D007070:Immunoglobulin A; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C084881:flt3 ligand protein; D010047:Ovalbumin