A protective role of locally administered immunostimulatory CpG oligodeoxynucleotide in a mouse model of genital herpes infection.
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.
Harandi
Ali M
AM
Department of Medical Microbiology & Immunology, Göteborg University Vaccine Research Institute, Göteborg University, Sweden. ali.harandi@microbio.gu.se
Eriksson
Kristina
K
Holmgren
Jan
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D018899:CpG Islands; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D017931:DNA Primers; D004195:Disease Models, Animal; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D017931:DNA Primers