Intranasal or Intragastric Immunization with Proteosome-ShigellaLipopolysaccharide Vaccines Protects Against Lethal Pneumonia in a Murine Model of Shigella Infection

摘要

Shigella sonnei and S. flexneri are major causes of bacillary dysentery anddiarrhea worldwide (15, 30). These organisms elicit inflammation by invading the colonic mucosa (14) Group-specific antibody recognizing the lipopolysaccharide (LPS) somatic antigen is associated with protection against shigellosis (3, 4, 31). Several vaccine approaches are under active investigation (10), including two types of parenteral subunit 0-antigen vaccines (16, 34). We have described subunit Shigella vaccines designed for mucosal delivery consisting of S. sonnei or S.flexneri. LPS complexed by hydrophobic interactions with meningococcal outer membrane protein prosomes (25, 26). Intranasal or intragastric immunization with these proteosome-LPS vaccines induces secretory immunoglobulin n A (IgA) and serum IgU in mice (25, 26) and protects guinea pigs against keratoconjunctivitis shigellosa (26). In the recent study we demonstrated the efficacy of the proteosome-vaccines in a murine intranasal challenge model (23, 35) Shigella infection. As confirmed by histopathologic analyses, intranasal or intragastric immunization with the protective vaccines protected mice against fatal suppurative pneumonia evoked by invasion of pulmonary mucosa by shigellae.