INTRANASAL AND INTRAMUSCULAR PROTEOSOME-STAPHYLOCOCCAL ENTEROTOXIN-B (SEB) TOXOID VACCINES - IMMUNOGENICITY AND EFFICACY AGAINST LETHAL SEBINTOXICATION IN MICE

Intranasal or intramuscular (i.m.) immunization of mice and i.m. immun ization of rabbits with formalinized staphylococcal enterotoxin B (SEB ) toroid in saline elicited higher anti-SEB serum immunoglobulin G (Ig G) titers when the toxoid was formulated with proteosomes. In addition , intranasal immunization of mice with this proteosome-toxoid vaccine elicited high levels of anti-SEB IgA in lung and intestinal secretions , whereas the toxoid without proteosomes did not. Two i.m. immunizatio ns with proteosome-toxoid plus alum also induced higher murine serum r esponses than alum-adjuvanted toxoid without proteosomes. Furthermore, proteosome-toxoid delivered intranasally in saline or i.m. with eithe r saline or alum afforded significant protection against lethal SEB ch allenge in two D-galactosamine-sensitized murine models of SEB intoxic ation, i.e., the previously described i.m. challenge model and a new r espiratory challenge model of mucosal SEB exposure, Efficacy correlate d with the induction of high serum levels of anti-SEB IgG. In contrast , intranasal or i.m. immunization with toxoid in saline without proteo somes was not significantly protective in either challenge model. Prot eosome-toxoid plus alum given i.m. also elicited more significant prot ection against respiratory challenge than the alum-adjuvanted toroid a lone. The capacity of proteosomes to enhance both i.m. and intranasal immunogenicity and efficacy of SEB toxoid indicates that testing such proteosome-SEB toxoid vaccines in the nonhuman primate aerosol challen ge model of SEB intoxication prior to immunogenicity trials in humans is warranted. These data expand the applicability of the proteosome mu cosal vaccine delivery system to protein toxoids and suggest that resp iratory delivery of proteosome vaccines may be practical for enhanceme nt of both mucosal and systemic immunity against toxic or infectious d iseases.