Jpn. J. Infect. Dis., 55, 37-44, 2002

To see an article, click this [PDF] link.

Invited Review

Discovery of Immunostimulatory CpG-DNA and Its Application to Tuberculosis Vaccine Development

Saburo Yamamoto¹*, Toshiko Yamamoto^1,2, Yasuhiro Nojima¹, Kiyoko Umemori¹, Susan Phalen², David N. McMurray², Etsuro Kuramoto³, Sumiko Iho⁴, Rumiko Takauji⁴, Yukio Sato⁵, Takeshi Yamada⁶, Naoya Ohara⁶, Sohkichi Matsumoto⁷, Yoshitaka Goto⁸, Kazuhiro Matsuo⁹ and Tohru Tokunaga¹⁰

¹National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, ²Texas A & M University Health Science Center, College Station, Texas, USA, ³Mitsui Pharmaceuticals, Inc., Togo, Mobara, Chiba 297-0017, ⁴Fukui Medical University School of Medicine, Matsuoka-cho, Yoshida, Fukui 910-1193, ⁵Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima 960-1295, ⁶Nagasaki University School of Dentistry, Sakamoto, Nagasaki 852-8523, ⁷Osaka City University School of Medicine, Asahi, Abeno-ku, Osaka 545-8585, ⁸Miyazaki University Faculty of Agriculture, Gakuen Kibanadai Nishi, Miyazaki 889-2192, ⁹Japan Science and Technology Cooperation, AIDS Vaccine Project Office, Nonthaburi 11000, Thailand and ¹⁰Fukuoka Jo-Gakuin University, Osa, Minami-ku, Fukuoka, 811-1313, Japan

(Received April 22, 2002)

CONTENTS:
1. Introduction 
2. Immunostimulatory sequences
3. Bacterial DNA, but not animal or plant DNA, possesses 
   immunostimulatory activity
4. Antitumor activity of immunostimulatory CpG-DNA
5. Immunostimulatory activity of CpG-DNA
6. Intracellular mechanisms of immunostimulatory CpG-DNA
7. Immunostimulatory CpG-DNA as an immunoadjuvant for vaccine development 
8. Therapeutic applications of immunostimulatory CpG-DNA

SUMMARY: DNA containing an unmethylated CpG motif has a potent immunostimulatory effect on the vertebrate immune system. Because such CpG motifs are relatively common in bacterial DNA, but rare in mammalian animal and plant DNA, they may be an evolutionary adaptation augmenting innate immunity, most likely in response to pathogens that replicate within the host cells, such as viruses and intracellular bacteria. Microbial infection induces innate immunity by triggering pattern-recognition systems. The infected cells produce proinflammatory cytokines that directly combat microbial invaders and express costimulating surface molecules, which develop adaptive immunity by inducing distinct T cell differentiation. Bacterial DNA with unmethylated CpG-DNA stimulates vertebrate immature immune cells to induce maturation and to produce TNF-α as well as Th1-type cytokines, IL-12 and IFN-γ. Therefore, CpG-DNA functions as an adjuvant for regulating the initiation of Th1 differentiation. The roles of immunostimulatory CpG motifs in DNA vaccine developments and in therapeutic applications have been discussed.

*Corresponding author: Tel: +81-42-561-0771, Fax: +81-42-565-3315, E-mail: saburo@nih.go.jp

Go to JJID Homepage                  Go to JJID 55(2) Contents