LOCAL IMMUNE-RESPONSE AND PROTECTION IN THE GUINEA-PIG KERATOCONJUNCTIVITIS MODEL-FOLLOWING IMMUNIZATION WITH SHIGELLA VACCINES

This study used the guinea pig keratoconjunctivitis model to examine t he importance of route of administration (mucosal versus parenteral), frequency and timing of immunization (primary versus boosting immuniza tion), and form of antigen given (live attenuated vaccine strain versu s O-antigen-protein conjugate) on the production of protective immunit y against Shigella infection. Since local immune response to the lipop olysaccharide (LPS) O-antigen of Shigella spp. is thought to be import ant for protection against disease, O-antigen-specific antibody-secret ing cells (ASC) in the spleen and regional lymph nodes of immunized an imals were measured by using an ELISPOT assay. Results indicated that protective efficacy was associated with a strong O-antigen-specific AS C response, particularly in the superficial ventral cervical lymph nod es draining the conjunctivae. In naive animals, a strong ASC response in the cervical lymph nodes and protection against challenge were dete cted only in animals that received a mucosal immunization. Protection in these animals was increased by a boosting mucosal immunization. Whi le parenteral immunization alone with an O-antigen-protein conjugate v accine did not protect naive animals against challenge, a combined par enteral-mucosal regimen elicited enhanced protection without the addit ion of a boosting immunization. Although O-antigen-specific serum immu noglobulin A titers were significantly higher in animals receiving a m ucosal immunization, there was no apparent correlation between levels of serum antibody and protection against disease.