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Effect of CpG Oligonucleotides on Vaccine-Induced B Cell Memory¹

National Cancer Institute, Frederick, MD 21702

Adding synthetic oligodeoxynucleotides containing unmethylated CpG motifs to Anthrax vaccine adsorbed (AVA, the licensed human vaccine) increases the speed and magnitude of the resultant Ab response. Ab titers persist in the protective range for >1 year, significantly longer than in animals vaccinated with AVA alone. Unexpectedly, a majority of mice immunized with CpG-adjuvanted AVA maintained resistance to anthrax infection even after their Ab titers had declined into the subprotective range. The survival of these animals was mediated by the de novo production of protective Abs by high affinity memory B cells re-stimulated immediately after challenge. Thus, a previously unrecognized benefit of CpG oligodeoxynucleotides adjuvants is their ability to expand the long-lived memory B cell population. Current findings demonstrate that CpG-adjuvanted AVA mediates protection both by stimulating a strong/persistent serum Ab response and by generating a high-affinity long-lived pool of memory B cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by the Joint Science and Technology Office for Chemical and Biological Defense of the Defense Threat Reduction Agency.

The assertions herein are the private ones of the authors and are not to be construed as official or as reflecting the views of Defense Threat Reduction Agency or the National Cancer Institute at large.

² Address correspondence and reprint requests to Dr. Dennis Klinman, Building 567 Room 205, National Cancer Institute, Frederick, MD 21702. E-mail address: klinmand{at}mail.nih.gov

³ Abbreviations used in this paper: PA, protective Ag; AVA, Anthrax vaccine adsorbed; ODN, oligodeoxynucleotide; SFT, splenic fragment technique.