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Journal of Virology, June 2006, p. 5283-5291, Vol. 80, No. 11
0022-538X/06/$08.00+0 doi:10.1128/JVI.02013-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Institute of Biomedicine, Department of Microbiology and Immunology, Sahlgrenska Academy at Göteborg University, Medicinaregatan 7A, Box 435, 413 46 Göteborg, Sweden,1 Department of Microbiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania2
Received 21 September 2005/ Accepted 15 February 2006
Although sexually transmitted pathogens are capable of inducing pathogen-specific immune responses, vaginal administration of nonreplicating antigens elicits only weak, nondisseminating immune responses. The present study was undertaken to examine the potential of CpG-containing oligodeoxynucleotide (CpG ODN) for induction of chemokine responses in the genital tract mucosa and also as a vaginal adjuvant in combination with glycoprotein D of herpes simplex virus type 2 (HSV-2) for induction of antigen-specific immune responses. We found that a single intravaginal administration of CpG ODN in mice stimulates a rapid and potent response of CC chemokines macrophage inflammatory protein 1
(MIP-1
), MIP-1ß, and RANTES as well as of CXC chemokines MIP-2 and IP-10 in the vagina and/or the genital lymph nodes. Importantly, intravaginal vaccination with recombinant gD2 in combination with CpG ODN gave rise to a strong antigen-specific Th1-like immune response in the genital lymph nodes as well as the spleens of the vaccinated mice. Further, such an immunization scheme conferred both systemic and mucosal immunoglobulin G antibody responses as well as protection against an otherwise lethal vaginal challenge with HSV-2. These results illustrate the potential of CpG ODN for induction of potent chemokine responses in the genital tract and also as a vaginal adjuvant for generation of Th1-type mucosal and systemic immune responses towards a nonreplicating antigen derived from a sexually transmitted pathogen. These data have implications for the development of a mucosal vaccine against genital herpes and possibly other sexually transmitted diseases.
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