Sequential B-Cell Epitopes ofBacillus anthracisLethal Factor Bind Lethal Toxin-Neutralizing Antibodies
| Autor: | A. Darise Farris, Jimmy D. Ballard, Judith A. James, Sherry R. Crowe, Simon Teryzan, Melissa L. Nguyen, Brian Cao, Sridevi Kurella |
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| Rok vydání: | 2009 |
| Předmět: |
Mice
Inbred A medicine.drug_class Bacterial Toxins Immunology Anthrax Vaccines Monoclonal antibody Microbiology Epitope Cell Line Anthrax Mice Antigen Neutralization Tests medicine Animals Neutralizing antibody Antigens Bacterial Anthrax vaccines biology Macrophages Antibodies Monoclonal biology.organism_classification Antibodies Bacterial Virology Bacillus anthracis Infectious Diseases Epitope mapping Polyclonal antibodies Immunoglobulin G Microbial Immunity and Vaccines biology.protein Epitopes B-Lymphocyte Female Parasitology Epitope Mapping |
| Zdroj: | Infection and Immunity. 77:162-169 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | The bipartite anthrax lethal toxin (LeTx) consisting of protective antigen (PA) and lethal factor (LF) is a major virulence factor contributing to death from systemicBacillus anthracisinfection. The current vaccine elicits antibodies directed primarily to PA; however, in experimental settings serologic responses to LF can neutralize LeTx and contribute to protection against infection. The goals of the present study were to identify sequential B-cell epitopes of LF and to determine the capacity of these determinants to bind neutralizing antibodies. Sera of recombinant LF-immunized A/J mice exhibited high titers of immunoglobulin G anti-LF reactivity that neutralized LeTx in vitro 78 days after the final booster immunization and protected the mice from in vivo challenge with 3 50% lethal doses of LeTx. These sera bound multiple discontinuous epitopes, and there were major clusters of reactivity on native LF. Strikingly, all three neutralizing, LF-specific monoclonal antibodies tested bound specific peptide sequences that coincided with sequential epitopes identified in polyclonal antisera from recombinant LF-immunized mice. This study confirms that LF induces high-titer protective antibodies in vitro and in vivo. Moreover, the binding of short LF peptides by LF-specific neutralizing monoclonal antibodies suggests that generation of protective antibodies by peptide vaccination may be feasible for this antigen. This study paves the way for a more effective anthrax vaccine by identifying discontinuous peptide epitopes of LF. |
| Databáze: | OpenAIRE |
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