Liposomal gD ectodomain (gD1–306 ) vaccine protects against HSV2 genital or rectal infection of female and male mice

• Published in: Vaccine 2009-12, Vol.28 (2), p.548-560
• Main Authors: Olson, K, Macias, P, Hutton, S, Ernst, W.A, Fujii, G, Adler-Moore, J.P
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animal models; Animals; Antibodies; Antigens; Clinical trials; Disease; E coli; Female; Females; g-Interferon; Gender differences; Genes; Genitalia - virology; Helper cells; Herpes Genitalis - immunology; Herpes Genitalis - prevention & control; Herpes simplex; Herpes Simplex Virus Vaccines - administration & dosage; Herpes Simplex Virus Vaccines - immunology; Herpesvirus 2, Human - immunology; HSV2 infection; Immunization; Infection; Infections; Interleukin 4; Lipids; Liposomal gD vaccine; Liposomes; Lymphocytes T; Male; Male and female mice; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Monophosphoryl lipid A; Proteins; Rectum; Rectum - virology; Rodents; Solvents; Spinal cord; Splenocytes; Studies; Survival; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.09.120

Abstract Herpes simplex virus type 2 (HSV2) is the most common causative agent of genital herpes, with infection rates as high as 1 in 6 adults. The present studies were done to evaluate the efficacy of a liposomal HSV2 gD1–306 vaccine (L-gD1–306 -HD) in an acute murine HSV2 infection model of intravaginal (female) or intrarectal (male or female) challenge. Two doses of L-gD1–306 -HD containing 60 μg gD1–306 -HD and 15 μg monophosphoryl lipid A (MPL) per dose provided protection against HSV2 intravaginal challenge (86–100% survival, P ≤ 0.0003 vs. control liposomes; P = 0.06 vs. L-gD1–306 -HD without MPL). Both male and female mice (BALB/c and C57BL/6) immunized with L-gD1–306 -HD/MPL were significantly protected against HSV2 intrarectal challenge, with higher survival rates compared to controls (71–100%, P ≤ 0.007). L-gD1–306 -HD/MPL also provided increased survival when compared to a liposomal peptide vaccine, L-gD264–285 -HD/MPL (male BALB/c, P ≤ 0.001; female BALB/c and male C57BL/6, P = 0.06). Mice given L-gD1–306 -HD/MPL also had minimal disease signs, reduced viral burden in their spinal cords and elevated neutralizing antibody titers in the females. The vaccine also stimulated gD1–306 -HD specific splenocytes of both male and female mice with significantly elevated levels of IFN-γ compared to IL-4 ( P ≤ 0.01) indicating that there was an enhanced Th1 response. These results provide the first evidence that the L-gD1–306 -HD vaccine can protect both male and female mice against intrarectal HSV2 challenge.