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 (β-galactosidase, β-gal) with immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) induces a mucosal IgA response equivalent to that induced by i.n. codelivery of β-gal with cholera toxin (CT). Furthermore, i.n. and intradermal (i.d.) delivery of the β-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 β-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.