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Journal of Virology, January 2003, p. 953-962, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.953-962.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Protective Role of Locally Administered Immunostimulatory CpG Oligodeoxynucleotide in a Mouse Model of Genital Herpes Infection

Ali M. Harandi,* Kristina Eriksson, and Jan Holmgren

Department of Medical Microbiology & Immunology, Göteborg University Vaccine Research Institute, Göteborg University, Göteborg, Sweden

Received 26 July 2002/ Accepted 8 October 2002

Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligodeoxynucleotides (ODNs) are known as potent activators of the immune system and inducers of several Th1-associated immunomodulatory cytokines. We therefore investigated whether such a CpG-containing ODN (CpG ODN) given mucosally in the female genital tract could enhance innate immunity and protect against genital herpes infection. Groups of C57BL/6 mice were treated intravaginally with either CpG ODN or a non-CpG ODN control in the absence of any antigen either 2 days before or 4 h after an intravaginal challenge with a normally lethal dose of herpes simplex virus type 2 (HSV-2). Mice treated with CpG ODN exhibited significantly decreased titers of HSV-2 in their vaginal fluids compared with non-CpG ODN-treated mice. Furthermore, CpG ODN pretreatment significantly protected against development of disease and death compared to non-CpG ODN pretreatment. Most strikingly, CpG ODN conferred protection against disease and death even when given after the viral challenge. The CpG ODN-induced protection was associated with a rapid production of gamma interferon (IFN-{gamma}), interleukin-12 (IL-12), IL-18, and RANTES in the genital tract mucosa following CpG ODN treatment. The observed protection appeared to be dependent on IFN-{gamma}, IL-12, IL-18, and T cells, as CpG ODN pretreatment did not confer any significant protection in mice deficient in IFN-{gamma}, IL-12, IL-18, or T cells. Further, a complete protective immunity to reinfection was elicited in CpG ODN-treated, HSV-2-challenged mice, suggesting a role for mucosally administered CpG ODN in inducing the development of an acquired immune response in addition to its potent stimulation of innate immunity.

* Corresponding author. Mailing address: Göteborg University Vaccine Research Institute (GUVAX), Department of Medical Microbiology & Immunology, Guldhedsgatan 10A, 413 46 Göteborg, Sweden. Phone: (46) 31-3424430. Fax: (46) 31-820160. E-mail: ali.harandi{at}microbio.gu.se.

Journal of Virology, January 2003, p. 953-962, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.953-962.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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