title: Intranasal immunization with CpG oligodeoxynucleotides as an adjuvant dramatically increases IgA and protection against herpes simplex virus-2 in the genital tract.
abstract: Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HSV and HIV, will likely be dependent on the induction of potent long-lasting mucosal immune responses in the genital tract. Recently, synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs were shown to serve as potent adjuvants for the induction of mucosal immune responses. Here, we show that intranasal immunization with CpG ODN, plus recombinant glycoprotein B (rgB) of HSV-1, results in significantly elevated levels of specific anti-gB IgA Abs in vaginal washes that remained high throughout the estrous cycle. Additionally, dramatically elevated numbers of specific IgA Ab-secreting cells were present and persisted in the genital tract in response to intravaginal (IVAG) HSV-2 challenge. HSV-2-specific CTL were observed at moderate levels in the spleens of CpG or non-CpG ODN-immunized mice. In contrast, strong CTL responses were observed locally in the genital tissues of both groups following IVAG HSV-2 challenge. Interestingly, mice immunized intranasally with rgB plus CpG ODN, but not non-CpG ODN, were significantly protected following IVAG HSV-2 challenge. Measurement of virus in protected CpG-immunized mice revealed a log lower level of replication within the first few days after infection. In conclusion, these results indicate that intranasal immunization with CpG ODN plus protein mediates immunity in the female genital tract capable of protecting against a sexually transmitted pathogen.
authors.affiliation: Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: W S
authors.initials: WS
authors.lastname: Gallichan
authors.forename: R N
authors.initials: RN
authors.lastname: Woolstencroft
authors.forename: T
authors.initials: T
authors.lastname: Guarasci
authors.forename: M J
authors.initials: MJ
authors.lastname: McCluskie
authors.forename: H L
authors.initials: HL
authors.lastname: Davis
authors.forename: K L
authors.initials: KL
authors.lastname: Rosenthal
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000282:Administration, Intravaginal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018899:CpG Islands / Q000276:immunology*; D004971:Estrus / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D022301:Herpes Simplex Virus Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus