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Efficacy and immunological comparison of the adjuvants MPL, MTP-PE, LT1, and CDN in gD3pep liposomes using the BALB/c mouse model of intravaginal HSV-1 infection
Herpes simplex virus type 1 (HSV-1) infects 47.8% of individuals ages 14 to 49 in the United States. This virus usually causes oral or eye mucosal infections, but is now responsible for nearly half of genital herpes infections. Presently, there is no vaccine to prevent infections. To test the efficacy of a liposomal vaccine containing three epitopes of the HSV-1 gD protein (gD3pep), we developed an HSV-1 intravaginal infection in BALB/c mice by challenging mice (n=5/group) with different concentrations of HSV-1 (F strain). Challenged mice were observed for morbidity and mortality for 11 days. The challenge dose that produced morbidity by day 6 or 7 was selected for subsequent testing with the liposomal gD3pep vaccine containing one of the following adjuvants: MPL, MTP-PE, LT1, or CDN. Phosphate buffered saline (PBS) was the control. Mice (n=14/group) received vaccine subcutaneously d0, d14, and d28. Spleens were harvested d31 (n=7/group) to determine IL-4 and IFN-γ secretion. Mice (n=7/group) were challenged intravaginally d35 with HSV-1 and monitored for morbidity and mortality to d63. Survival was 86% with CDN, 71% with MPL, 57% with MTP-PE, and 14% with both LT1 and PBS. Disease signs and weight loss paralleled survival. IL-4 secreting splenocytes (Th1 response) were significantly higher in MTP-PE and CDN groups (p≥0.0099), while the MPL group had higher IFN-γ secreting splenocytes (Th2 response). CDN, MPL, and MTP-PE adjuvants protected mice against HSV-1 infection, via different immune response mechanisms suggesting that a Th1 or Th2 response can generate protection against genital HSV-1 infection.