A combination of Flt3 ligand cDNA and CpG oligodeoxynucleotide as nasal adjuvant elicits protective secretory-IgA immunity to Streptococcus pneumoniae in aged mice.
Our previous study showed that a combination of a plasmid-expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotides (CpG ODN) as a combined nasal adjuvant elicited mucosal immune responses in aged (2-y-old) mice. In this study, we investigated whether a combination of pFL and CpG ODN as a nasal adjuvant for a pneumococcal surface protein A (PspA) would enhance PspA-specific secretory-IgA Ab responses, which could provide protective mucosal immunity against Streptococcus pneumoniae infection in aged mice. Nasal immunization with PspA plus a combination of pFL and CpG ODN elicited elevated levels of PspA-specific secretory-IgA Ab responses in external secretions and plasma in both young adult and aged mice. Significant levels of PspA-specific CD4(+) T cell proliferative and PspA-induced Th1- and Th2- type cytokine responses were noted in nasopharyngeal-associated lymphoreticular tissue, cervical lymph nodes, and spleen of aged mice, which were equivalent to those in young adult mice. Additionally, increased numbers of mature-type CD8, CD11b-expressing dendritic cells were detected in mucosal inductive and effector lymphoid tissues of aged mice. Importantly, aged mice given PspA plus a combination of pFL and CpG ODN showed protective immunity against nasal S. pneumoniae colonization. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for protection against S. pneumoniae in the elderly.
Department of Pediatric Dentistry, Immunobiology Vaccine Center, Institute of Oral Health Research, University of Alabama at Birmingham, AL 35294-0007, USA.
Yoshiko
Y
Fukuyama
Janice D
JD
King
Kosuke
K
Kataoka
Ryoki
R
Kobayashi
Rebekah S
RS
Gilbert
Susan K
SK
Hollingshead
David E
DE
Briles
Kohtaro
K
Fujihashi
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000097:blood; D000375:Aging / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D018076:DNA, Complementary / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D004338:Drug Combinations; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis* / Q000502:physiology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000097:blood / Q000235:genetics*; D051379:Mice; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D018076:DNA, Complementary; D004338:Drug Combinations; D007071:Immunoglobulin A, Secretory; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C084881:flt3 ligand protein; C051592:pneumococcal surface protein A