An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor
| Autor: | Helen C. Flick-Smith, Brendan N. Neeson, Rebecca J. Ingram, Daniel M. Altmann, Stephen James Moore, Liliana Rodriguez, Helen S. Atkins, Les Baillie, Marcela F. Pasetti, Theresa B. Huwar, Dominic C. Jenner, Gabriela Mellado-Sánchez, James P. Nataro |
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| Rok vydání: | 2010 |
| Předmět: |
Recombinant Fusion Proteins
T-Lymphocytes Bacterial Toxins Anthrax Vaccines Biology Article Immunoglobulin G Microbiology Mice Antigen Animals Humans Antigens Bacterial Mice Inbred BALB C Anthrax vaccines General Veterinary General Immunology and Microbiology Immunogenicity Public Health Environmental and Occupational Health biology.organism_classification Antibodies Bacterial Antibodies Neutralizing Virology Bacillus anthracis Vaccination Infectious Diseases biology.protein Molecular Medicine Female Bacterial antigen Antibody |
| Zdroj: | Vaccine. 28:6740-6748 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2010.07.075 |
| Popis: | Studies have confirmed the key role of Bacillus anthracis protective antigen (PA) in the US and UK human anthrax vaccines. However, given the tripartite nature of the toxin, other components, including lethal factor (LF), are also likely to contribute to protection. We examined the antibody and T cell responses to PA and LF in human volunteers immunized with the UK anthrax vaccine (AVP). Individual LF domains were assessed for immunogenicity in mice when given alone or with PA. Based on the results obtained, a novel fusion protein comprising D1 of LF and the host cell-binding domain of PA (D4) was assessed for protective efficacy. Murine protection studies demonstrated that both full-length LF and D1 of LF conferred complete protection against a lethal intraperitoneal challenge with B. anthracis STI spores. Subsequent studies with the LFD1-PAD4 fusion protein showed a similar level of protection. LF is immunogenic in humans and is likely to contribute to the protection stimulated by AVP. A single vaccine comprising protective regions from LF and PA would simplify production and confer a broader spectrum of protection than that seen with PA alone. |
| Databáze: | OpenAIRE |
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