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Infection and Immunity, November 1999, p. 5658-5663, Vol. 67, No. 11
0019-9567/99/$04.00+0

Repeated Administration of Synthetic Oligodeoxynucleotides Expressing CpG Motifs Provides Long-Term Protection against Bacterial Infection

Dennis M. Klinman,* Jackie Conover, and Cevahir Coban

Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland

Received 24 May 1999/Returned for modification 29 June 1999/Accepted 9 August 1999

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.

* Corresponding author. Mailing address: Bldg. 29A Rm. 3 D 10, CBER/FDA Bethesda, MD 20892. Phone: (301) 827-1707. Fax: (301) 496-1810. E-mail: Klinman{at}CBER.FDA.GOV.

Infection and Immunity, November 1999, p. 5658-5663, Vol. 67, No. 11
0019-9567/99/$04.00+0


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