Immunostimulatory DNA is a potent mucosal adjuvant.
Most proteins delivered to mucosal surfaces fail to induce mucosal or systemic immune responses. We demonstrate that a single intranasal (i.n.) coadministration of a model antigen (beta-galactosidase, beta-gal) with immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) induces a mucosal IgA response equivalent to that induced by i.n. codelivery of beta-gal with cholera toxin (CT). Furthermore, i.n. and intradermal (i.d.) delivery of the beta-gal/ISS-ODN mix stimulates equivalent Th1-biased systemic immune responses with high-level cytotoxic T lymphocyte (CTL) activity. In contrast, i.n. immunization with beta-gal and CT results in a Th2-biased systemic immune response with poor CTL activity. Our data show that i.n. delivery of ISS-ODN provides effective adjuvant activity for the induction of both mucosal and systemic Th1-biased immune responses. This immunization approach deserves consideration in the development of vaccines against mucosal pathogens.
Horner
A A
AA
Department of Medicine, and The Sam and Rose Stein Institute for Aging, University of California at San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0663, USA. aahorn@aol.com
Ronaghy
A
A
Cheng
P M
PM
Nguyen
M D
MD
Cho
H J
HJ
Broide
D
D
Raz
E
E
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001483:Base Sequence; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D009838:Oligodeoxyribonucleotides; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA; D002772:Cholera Toxin; D001616:beta-Galactosidase