Anthrax Protective Antigen Delivered by Salmonella enterica Serovar Typhi Ty21a Protects Mice from a Lethal Anthrax Spore Challenge
| Autor: | Dennis J. Kopecko, Tod J. Merkel, Yanping Wu, Siba Bhattacharyya, Milan S. Blake, Sunil Singh, Manuel Osorio |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Recombinant Fusion Proteins
Ty21a Bacterial Toxins Genetic Vectors Immunology Anthrax Vaccines Salmonella typhi Microbiology Cell Line Anthrax Hemolysin Proteins Mice Antigen Antibody Specificity Immunity Animals Humans Spores Bacterial Antigens Bacterial Anthrax vaccines biology Escherichia coli Proteins biology.organism_classification Antibodies Bacterial Virology Bacillus anthracis Vaccination Infectious Diseases Immunoglobulin G Microbial Immunity and Vaccines Typhoid vaccine Female Immunization Parasitology Plasmids |
| Zdroj: | Infection and Immunity. 77:1475-1482 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00828-08 |
| Popis: | Bacillus anthracis , the etiological agent of anthrax disease, is a proven weapon of bioterrorism. Currently, the only licensed vaccine against anthrax in the United States is AVA Biothrax, which, although efficacious, suffers from several limitations. This vaccine requires six injectable doses over 18 months to stimulate protective immunity, requires a cold chain for storage, and in many cases has been associated with adverse effects. In this study, we modified the B. anthracis protective antigen (PA) gene for optimal expression and stability, linked it to an inducible promoter for maximal expression in the host, and fused it to the secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA) on a low-copy-number plasmid. This plasmid was introduced into the licensed typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and was found to be genetically stable. Immunization of mice with three vaccine doses elicited a strong PA-specific serum immunoglobulin G response with a geometric mean titer of 30,000 (range, 5,800 to 157,000) and lethal-toxin-neutralizing titers greater than 16,000. Vaccinated mice demonstrated 100% protection against a lethal intranasal challenge with aerosolized spores of B. anthracis 7702. The ultimate goal is a temperature-stable, safe, oral human vaccine against anthrax infection that can be self-administered in a few doses over a short period of time. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|