Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection.
Synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate an innate immune response characterized by the production of polyreactive immunoglobulin M antibodies and immunomodulatory cytokines. This immune response has been shown to protect mice from challenge by Listeria monocytogenes and Francisella tularensis for up to 2 weeks. By repeatedly administering CpG ODN two to four times/month, we found that this protection could be maintained indefinitely. Protection was associated with a significant increase in the number of spleen cells that could be triggered by subsequent pathogen exposure to secrete gamma interferon and interleukin-6 in vivo (P < 0.01). ODN-treated animals remained healthy and developed neither macroscopic nor microscopic evidence of tissue damage or inflammation. Thus, repeated administration of CpG ODN may provide a safe means of conferring long-term protection against infectious pathogens.
Klinman
D M
DM
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland. Klinman@CBER.FDA.GOV
Conover
J
J
Coban
C
C
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008088:Listeriosis / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D014406:Tularemia / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D015226:Dinucleoside Phosphates; D007371:Interferon-gamma; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; C015772:CpG dinucleotide