Towards a human oral vaccine for anthrax: The utility of a Salmonella Typhi Ty21a-based prime-boost immunization strategy
Autor: | Helen S. Atkins, Stephen James Moore, James P. Nataro, Chiguang Feng, Ana L. Rodriguez, Leslie W.J. Baillie, Marcela F. Pasetti |
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Rok vydání: | 2008 |
Předmět: |
Salmonella
Ty21a Anthrax toxin Immunization Secondary Administration Oral Anthrax Vaccines Salmonella typhi medicine.disease_cause complex mixtures Article Microbiology Anthrax Mice Adjuvants Immunologic Neutralization Tests medicine Animals Humans Codon Administration Intranasal Immunization Schedule Spores Bacterial Mice Inbred BALB C Anthrax vaccines General Veterinary General Immunology and Microbiology biology Public Health Environmental and Occupational Health biology.organism_classification Antibodies Bacterial Virology Bacillus anthracis Infectious Diseases Salmonella enterica Immunoglobulin G Typhoid vaccine Alum Compounds bacteria Molecular Medicine Female Immunization |
Zdroj: | Vaccine. 26:6083-6091 |
ISSN: | 0264-410X |
Popis: | We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [Stokes MG, Titball RW, Neeson BN, et al. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infect Immun 2007;75(April (4)):1827-34]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax. |
Databáze: | OpenAIRE |
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