1. Field of the Invention
The present invention relates to a method for inducing mucosal immunity which comprises a nucleic acid containing immunostimulatory DNA sequence (ISS) to human mucosal membrane.
2. Related Art Statement
Throughout the history of genetic recombinant technology, plasmid DNA (pDNA) of bacterial origin has been recognized to be essential for cloning of useful genes and for mass production of useful proteins.
As a new application of these pDNAs, DNA vaccination has been proposed. This technology is based on the finding that by direct injection of pDNA with antigenic protein-encoding gene into the quadriceps femoris muscle of mice, a protein encoded by pDNA was expressed in the muscle cells and induced an immune response to the expressed protein.
Following the above finding, it has been reported that oligonucleotides (ODNs) containing a two base sequence of unmethylated cytosine and guanine next thereto (CpG motifs), which are present in bacterial DNA, or CpG motif-containing pDNAs themselves stimulate lymphocytes/monocytes to induce several cytokines such as interleukin 6 and interleukin 12 (Pisetsky S. D. et al., J. Immunol, 156, 421, 1996). These DNA sequences, termed immunostimulatory DNA sequences (ISSs), have been reported to have the function of inducing the production of T helper-1 (Th1) type cytokines by monocytes. It is known that the Th1 type systemic immunity can be induced by injection of pDNA with ISS through production of interferon .gamma. (IFN-.gamma.) or interleukin 12 (IL-12) stimulated by ISS in pDNA (Sato Y., et al., Science, 273, 352, 1996).