Mucosal administration of CpG oligodeoxynucleotide elicits strong CC and CXC chemokine responses in the vagina and serves as a potent Th1-tilting adjuvant for recombinant gD2 protein vaccination against genital herpes.
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 1alpha (MIP-1alpha), MIP-1beta, 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.
Tengvall
Sara
S
Institute of Biomedicine, Department of Microbiology and Immunology, Vaccine Research Institute (GUVAX), Sahlgrenska Academy at Göteborg University, Medicinaregatan 7A, 413 46 Göteborg, Sweden.
Lundqvist
Annika
A
Eisenberg
Roselyn J
RJ
Cohen
Gary H
GH
Harandi
Ali M
AM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018925:Chemokines; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2