Efficacy Against Vaginal Herpes Virus Infection By Lipidated Or Non-Lipidated Tucaresol Adjuvants In A Herpes GD Tripeptide Liposomal Vaccine
Herpes Simplex Virus 2 (HSV-2) causes recurrent genital lesions. This study examined the efficacy against murine vaginal Herpes infection using an HSV-2 gD tripeptide (gD3pep) liposomal vaccine (LV) with Lipidated or Non-Lipidated Tucaresol (LipT or NLipT) adjuvants. Methods: LV or phosphate buffer (PBS) were administered 3X subcutaneously(SQ) to BALB/c mice on d0, d28, d56. LV contained gD3pep (15μg/dose) and LipT (3μg or 5.6μg/dose), NLipT (5.6μg/dose), MPL (monophosphoryl Lipid A,15μg/dose) or LipT (3ug/dose) plus MPL (7.5ug/dose); controls were LipT or NLipT (5.6μg/dose) without gD3pep, or PBS. Medroxyprogestrone was given SQ d63 and d69 to enhance virus infectivity and mice challenged intravaginally with HSV-2, d70. Disease signs and morbidity were monitored 2X/day for 28 days. Vaginal swabs collected d72 were analyzed for vaginal viral burden. Results: Survival with gD3pep and LipT (3ug/dose) plus MPL (7.5ug/dose) (100%), MPL (15ug/dose) (100%) or LipT(5.6μg/dose) (90%) was significantly better than vaccination with NLipT (5.6μg/dose) with no protein (11%) or PBS (0%) (¬¬p <.0047). Disease signs and viral burden paralleled survival data. There was also a significant difference in viral burden between the gD3pep liposomes having different LipT doses or the combination of LipT plus MPL versus PBS (p<0.0129). Conclusions: gD3pep liposomes containing LipT at 5.6μg/dose, LipT (3ug/dose) plus MPL (7.5ug/dose) or MPL (15ug/dose) each generated significant protection against a murine intravaginal HSV-2 challenge. The marked efficacy seen using the combination of LipT plus MPL at lower doses, indicate that these adjuvants are not antagonistic and may further enhance the immune response when used in combination.
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