Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection

Synthetic oligodeoxynucleotides (ODN) expressing unmethylated CPS motifs st imulate an innate immune response characterized by the production of polyre active immunoglobulin M antibodies and immunomodulatory cytokines. This imm une response has been shown to protect mice from challenge by Listeria mono cytogenes and Francisella tularensis for up to 2 weeks. By repeatedly admin istering CpG ODN two to four times/month, we found that this protection cou ld be maintained indefinitely. Protection was associated with a significant increase in the number of spleen cells that could be triggered by subseque nt pathogen exposure to secrete gamma interferon and interleukin-6 in vivo (P < 0.01). ODN-treated animals remained healthy and developed neither macr oscopic nor microscopic evidence of tissue damage or inflammation. Thus, re peated administration of CpG ODN may provide a safe means of conferring lon g-term protection against infectious pathogens.