title: Intranasal and intramuscular proteosome-staphylococcal enterotoxin B (SEB) toxoid vaccines: immunogenicity and efficacy against lethal SEB intoxication in mice.
abstract: Intranasal or intramuscular (i.m.) immunization of mice and i.m. immunization of rabbits with formalinized staphylococcal enterotoxin B (SEB) toxoid in saline elicited higher anti-SEB serum immunoglobulin G (IgG) 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. immunizations with proteosome-toxoid plus alum also induced higher murine serum responses than alum-adjuvanted toxoid without proteosomes. Furthermore, proteosome-toxoid delivered intranasally in saline or i.m. with either saline or alum afforded significant protection against lethal SEB challenge in two D-galactosamine-sensitized murine models of SEB intoxication, i.e., the previously described i.m. challenge model and a new respiratory challenge model of mucosal SEB exposure. Efficacy correlated with the induction of high serum levels of anti-SEB IgG. In contrast, intranasal or i.m. immunization with toxoid in saline without proteosomes was not significantly protective in either challenge model. Proteosome-toxoid plus alum given i.m. also elicited more significant protection against respiratory challenge than the alum-adjuvanted toxoid alone. 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 challenge model of SEB intoxication prior to immunogenicity trials in humans is warranted. These data expand the applicability of the proteosome mucosal vaccine delivery system to protein toxoids and suggest that respiratory delivery of proteosome vaccines may be practical for enhancement of both mucosal and systemic immunity against toxic or infectious diseases.
authors.affiliation: Division of Pathology, Walter Reed Army Institute of Research, Washington, DC 20307, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Lowell
authors.forename: R W
authors.initials: RW
authors.lastname: Kaminski
authors.forename: S
authors.initials: S
authors.lastname: Grate
authors.forename: R E
authors.initials: RE
authors.lastname: Hunt
authors.forename: C
authors.initials: C
authors.lastname: Charney
authors.forename: S
authors.initials: S
authors.lastname: Zimmer
authors.forename: C
authors.initials: C
authors.lastname: Colleton
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D001980:Bronchi / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology* / Q000633:toxicity*; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007273:Injections, Intramuscular; D007422:Intestines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009097:Multienzyme Complexes / Q000008:administration & dosage / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D011817:Rabbits; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004768:Enterotoxins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009097:Multienzyme Complexes; C031818:enterotoxin B, staphylococcal; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex