Immunogenicity and efficacy against lethal aerosol staphylococcal enterotoxin B challenge in monkeys by intramuscular and respiratory delivery of proteosome-toxoid vaccines.
Staphylococcal enterotoxin B (SEB), a primary cause of food poisoning, is also a superantigen that can cause toxic shock after traumatic or surgical staphylococcal wound [correction of would] infections or viral influenza-associated staphylococcal superinfections or when aerosolized for use as a potential biologic warfare threat agent. Intranasal or intramuscular (i.m.) immunization with formalinized SEB toxoid formulated with meningococcal outer membrane protein proteosomes has previously been shown to be immunogenic and protective against lethal respiratory or parenteral SEB challenge in murine models of SEB intoxication. Here, it is demonstrated that immunization of nonhuman primates with the proteosome-SEB toxoid vaccine is safe, immunogenic, and protective against lethal aerosol challenge with 15 50% lethal doses of SEB. Monkeys (10 per group) were primed i.m. and given booster injections by either the i.m. or intratracheal route without adverse side effects. Anamnestic anti-SEB serum immunoglobulin G (IgG) responses were elicited in all monkeys, but strong IgA responses in sera and bronchial secretions were elicited both pre- and post-SEB challenge only in monkeys given booster injections intratracheally. The proteosome-SEB toxoid vaccine was efficacious by both routes in protecting 100% of monkeys against severe symptomatology and death from aerosolized-SEB intoxication. These data confirm the safety, immunogenicity, and efficacy in monkeys of parenteral and respiratory vaccination with the proteosome-SEB toxoid, thereby supporting clinical trials of this vaccine in humans. The safety and enhancement of both bronchial and systemic IgA and IgG responses by the proteosome vaccine delivered by a respiratory route are also encouraging for the development of mucosally delivered proteosome vaccines to protect against SEB and other toxic or infectious respiratory pathogens.
Division of Pathology, Walter Reed Army Institute of Research, Washington, D.C. 20307, USA.
G H
GH
Lowell
C
C
Colleton
D
D
Frost
R W
RW
Kaminski
M
M
Hughes
J
J
Hatch
C
C
Hooper
J
J
Estep
L
L
Pitt
M
M
Topper
R E
RE
Hunt
W
W
Baker
W B
WB
Baze
D000336:Aerosols; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001980:Bronchi / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology* / Q000633:toxicity; D005260:Female; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D013208:Staphylococcal Toxoid / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology* / Q000633:toxicity; D014132:Trachea; D014611:Vaccination / Q000379:methods
D000336:Aerosols; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004768:Enterotoxins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D013208:Staphylococcal Toxoid; D018089:Superantigens; C031818:enterotoxin B, staphylococcal