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Use of CpG oligodeoxynucleotides as immune adjuvants

Authors

  • Dennis M. Klinman,

    Corresponding author
    1. Section of Retroviral Immunology, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
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  • Debra Currie,

    1. Section of Retroviral Immunology, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
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  • Ihsan Gursel,

    1. Section of Retroviral Immunology, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
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  • Daniela Verthelyi

    1. Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
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Dennis M. Klinman
Building 29A, Room 3D10
Division of Viral Products
CBER, FDA
8800 Rockville Pike
Bethesda, MD 20892
USA
Tel.: +1 301 827 1707
Fax: +1 301 496 1810
E-mail: klinman@cber.fda.gov

Abstract

Summary:  Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs directly stimulate human B cells and plasmacytoid dendritic cells (pDCs), thereby promoting the production of T helper 1 (Th1) and pro-inflammatory cytokines and the maturation/activation of professional antigen-presenting cells. These activities enable CpG ODNs to act as immune adjuvants, accelerating and boosting antigen-specific immune responses by 5–500-fold. These effects are optimized by maintaining close physical contact between the CpG DNA and the immunogen. Animal challenge models establish that protective immunity can be accelerated and magnified by coadministering CpG DNA with vaccines. Ongoing clinical studies indicate that CpG ODNs are safe and well tolerated when administered as adjuvants to humans, and in some cases, they increase vaccine-induced immune responses.

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