title: Lipid A mimetics are potent adjuvants for an intranasal pneumonic plague vaccine.
abstract: An effective intranasal (i.n.) vaccine against pneumonic plague was developed. The formulation employed two synthetic lipid A mimetics as adjuvant combined with Yersinia pestis-derived V- and F1-protective antigens. The two nontoxic lipid A mimetics, classed as amino-alkyl glucosaminide 4-phosphates (AGPs) are potent ligands for the Toll-like receptor (TLR) 4. Using a murine (BALB/c) pneumonic plague model, we showed a single i.n. application of the vaccine provided 63% protection within 21 days against a Y. pestis CO92 100 LD50 challenge. Protection reached 100% by 150 days. Using a homologous i.n. 1 degrees /2 degrees dose regimen, with the boost administered at varying times, 63% protection was achieved within 7 days and 100% protection was achieved by 21 days after the first immunization. Little or no protection was observed in animals that received antigens alone, and no protection was observed when the vaccine was administered to BALB/c TLR4 mutant mice. Vaccine-induced serum IgG titers to F1 and V-antigen were reflected in high titers for IgG1 and IgG2a, the latter reflecting a bias for a cell-mediated (TH1) immune response. This intranasal vaccine showed 90% protection in Sprague-Dawley rats challenged with 1000 LD50. We conclude that lipid A mimetics are highly effective adjuvants for an i.n. plague vaccine.
authors: Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, 142 Life Science, Moscow, ID 83844-3052, United States.
authors: Christina L
authors: CL
authors: Airhart
authors: Harold N
authors: HN
authors: Rohde
authors: Carolyn J
authors: CJ
authors: Hovde
authors: Gregory A
authors: GA
authors: Bohach
authors: Claudia F
authors: CF
authors: Deobald
authors: Stephen S
authors: SS
authors: Lee
authors: Scott A
authors: SA
authors: Minnich
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005944:Glucosamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000276:immunology; D006801:Humans; D008050:Lipid A / Q000737:chemistry / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D010930:Plague / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D008050:Lipid A; D010931:Plague Vaccine; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D005944:Glucosamine