Mucosal delivery of herpes simplex virus vaccine

Abstract

The mucosal route for the production of mucosal and systemic herpes simplex virus (HSV) antibodies was investigated using HSV1 subunit vaccine administered to guinea pigs. Groups of test animals (n = 13) were dosed, nasally or vaginally and compared with those injected subcutaneously (s.c.). The vaccines, in aqueous or gel form, were administered 5 and 3 weeks prior to vaginal challenge with HSV2 suspension. Control infected and non-infected animals were included for comparison. Animals which were vaccinated s.c. were shown to respond to subsequent infection with HSV by the production of serum HSV-specific IgG (and IgA) but negligible amounts of vaginal IgG and IgA. Control non-infected and infected-only groups produced none and only a small amount of vaginal HSV-specific antibodies, respectively. Substantial protection against HSV2 infection of the female guinea pig genital tract was provided by s.c. immunization with HSV vaccine. Protection was evaluated in terms of the reduction of histopathological lesions and clinical signs in vaccinated and control animals. The serum humoral response to nasal delivery in phosphate-buffered saline was comparable, and was superior for vaginal washes to that of parenteral vaccination. The nasally delivered free antigen gave significant (p < or = 0.05) reduction in the severity of the disease and higher levels of specific serum and vaginal immunoglobulin antibodies to HSV when compared with non-immunized infected-only controls, probably due to uptake of antigenically intact protein. Vaginal gel treatment slightly reduced the severity of the illness and gave higher humoral responses than those induced by vaginally delivered free antigen. Findings also indicate that these mucosal immune responses were produced at a site distant from the site of vaccination, suggesting a common immunological system.