Lipid A mimetics are potent adjuvants for an intranasal pneumonic plague vaccine
| Autor: | Carolyn J. Hovde, Stephen S. Lee, Scott A. Minnich, Gregory A. Bohach, Claudia F. Deobald, Christina L. Airhart, Harold N. Rohde |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Pneumonic plague Yersinia pestis medicine.medical_treatment Biology Bubonic plague Article Microbiology Rats Sprague-Dawley Lipid A Mice Immune system Adjuvants Immunologic medicine Animals Humans Administration Intranasal Glucosamine Mice Inbred BALB C Plague Plague Vaccine General Veterinary General Immunology and Microbiology Molecular Mimicry Public Health Environmental and Occupational Health Yersiniosis biology.organism_classification medicine.disease Antibodies Bacterial Virology Rats Toll-Like Receptor 4 Disease Models Animal Infectious Diseases Molecular Medicine Plague vaccine Female Adjuvant |
| Zdroj: | Vaccine. 26:5554-5561 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2008.08.007 |
| Popis: | 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 LD 50 challenge. Protection reached 100% by 150 days. Using a homologous i.n. 1°/2° 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 (T H 1) immune response. This intranasal vaccine showed 90% protection in Sprague–Dawley rats challenged with 1000 LD 50 . We conclude that lipid A mimetics are highly effective adjuvants for an i.n. plague vaccine. |
| Databáze: | OpenAIRE |
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