A RECOMBINANT SALMONELLA-TYPHIMURIUM VACCINE INDUCES LOCAL IMMUNITY BY 4 DIFFERENT ROUTES OF IMMUNIZATION

Immunization of mice with an attenuated Salmonella typhimurium strain (Phop(c)) carrying a plasmid encoding a hybrid form of the hepatitis B virus core antigen (HBc) induced specific antibody responses against the bacterial lipopolysaccharide (LPS) and HBc. Different mucosal rout es of immunization, i.e., oral, nasal, rectal, and vaginal, were compa red for their ability to induce a systemic as well as a mucosal respon se at sites proximal or distant to the site of immunization. Anti-LPS and anti-HBc immunoglobulin A (IgA) antibodies were measured in saliva , in feces, and in genital, bronchial, and intestinal secretions, Spec ific antibodies in serum and secretions were observed after immunizati on via all routes; however, the response to LPS was independent of tha t against HBc. In serum, Saliva, and genital and bronchial secretions, high amounts of anti-HBc IgA were obtained by the nasal route of immu nization, Vaginal immunization resulted in two different responses in mice: high and low. We observed a correlation between the level of spe cific immune response and the estrous status of these mice at the time of immunization, Rectal immunization induced high amounts of IgA agai nst HBc and LPS in colonorectal secretions and feces but not at distan t sites. These data suggest that S. typhimurium is able to invade diff erent mucosal tissues and induce long-lasting local IgA responses agai nst itself and a carried antigen after a single immunization.