Abstract |
The mammalian innate immune system recognizes pathogens via a series of pattern-recognition receptors such as the toll-like receptors (TLR) that interact with pathogen-associated molecular patterns ( PAMPs) and lead to the rapid activation of innate immune cells. In this study, we compared the efficacy of CpG ODN (a TLR9 agonist) and resiquimod ( R-848; a TLR7/8 agonist) for topical immunoprophylaxis or immunotherapy of vaginal herpes simplex virus type 2 (HSV-2) infection in mice. Efficacy against HSV infection was observed with CpG ODN but less so with R-848, even after repeated administrations. Intravaginal (IVAG) administration of CpG ODN resulted in strong local but relatively weak systemic immune activation, as determined by levels of the chemokines IP-10, MIG and I-TAC in vaginal tissue and plasma, respectively. In contrast, IVAG administration of R-848 resulted in high levels of plasma IP-10, similar to those seen after parenteral administration, but overall, weaker or shorter-lived local immune responses than obtained with CpG ODN. These findings suggest that differences in biodistribution and sites of immune activation between CpG ODN and R-848 after IVAG delivery account for differences in efficacy, and demonstrate the need for local mucosal innate activation for protection against HSV-2.
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Authors | Michael J McCluskie, Janna L M Cartier, Amy J Patrick, Dusan Sajic, Risini D Weeratna, Kenneth L Rosenthal, Heather L Davis |
Journal | Antiviral research
(Antiviral Res)
Vol. 69
Issue 2
Pg. 77-85
(Feb 2006)
ISSN: 0166-3542 [Print] Netherlands |
PMID | 16377001
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Adjuvants, Immunologic
- CPG-oligonucleotide
- Imidazoles
- Oligodeoxyribonucleotides
- resiquimod
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Topics |
- Adjuvants, Immunologic
(administration & dosage, therapeutic use)
- Animals
- CpG Islands
- Female
- Herpes Genitalis
(drug therapy, prevention & control, virology)
- Herpesvirus 2, Human
(drug effects, pathogenicity)
- Imidazoles
(administration & dosage, therapeutic use)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Oligodeoxyribonucleotides
(administration & dosage, therapeutic use)
- Treatment Outcome
- Vagina
(virology)
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