Analysis of epitope information related toBacillus anthracisandClostridium botulinum

Abstract

We have reviewed the information about epitopes of immunological interest from Clostridium botulinum and Bacillus anthracis, by mining the Immune Epitope Database and Analysis Resource. For both pathogens, the vast majority of epitopes reported to date are derived from a single protein: the protective antigen of B. anthracis and the neurotoxin type A of C. botulinum. A detailed analysis of the data was performed to characterize the function, localization and conservancy of epitopes identified as neutralizing and/or protective. In order to broaden the scope of this analysis, we have also included data describing immune responses against defined fragments (over 50 amino acids long) of the relevant antigens. The scarce information on T-cell determinants and on epitopes from other antigens besides the toxins, highlights a gap in our knowledge and identifies areas for future research. Despite this, several distinct structures at the epitope and fragment level are described herein, which could be potential additions to future vaccines or targets of novel immunotherapeutics and diagnostic reagents. Keywordsanthrax toxin; Bacillus anthracis; botulinum toxin; Clostridium botulinum; epitope; therapeutic antibodies; vaccine Bacillus anthracis and Clostridium botulinum are Gram-positive soil-dwelling bacteria. B. anthracis is a relatively common veterinary pathogen that has emerged recently as a major biological weapon. By contrast, C. botulinum does not cause invasive disease but produces a potent neurotoxin that has both therapeutic and weapon potential [1,2]. Given their potential importance as biological weapons, there is intense interest in the generation of vaccines, passive antibody therapies and immune-based diagnostic strategies against both B. anthracis and the C. botulinum toxin [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Information related to immune epitopes can be used to advance our understanding of disease pathogenesis and host immunity, as well as applied to the development and characterization of therapeutics and diagnostics, including the establishment of reliable correlates of protection to monitor their performance. This review aims to provide a comprehensive panorama on the current status of knowledge specific to epitopes from these pathogens and to identify areas where additional study is needed.Bioinformatic tools have greatly enhanced our ability to both catalog and analyze vast amounts of scientific data. The performance of meta-analyses from the data can facilitate indepth evaluation of existing knowledge in a particular area of research [15]. The Immune Epitope Database and Analysis Resource (IEDB) [101] is a project that is hosted by scientists at the La Jolla Institute for Allergy and Immunology with support from the National Institute of Allergy and Infectious Diseases, a part of the US NIH. The goal of the IEDB is to compile and present immunological data and analysis tools through a single interface [16]. The scope of the IEDB encompasses structures that are targets of adaptive...

Purification, Modeling, and Analysis of Botulinum Neurotoxin Subtype A5 (BoNT/A5) from Clostridium botulinum Strain A661222

“…Four different regions in the HC of the protein were selected for analysis (Table 1). These peptides are known to be important for antibody recognition since they were previously character-ized as highly sensitive epitopes (2,7,10,13,17,19). The antibodies generated against A1 could be significantly affected by the differences in these regions, even though the identity of the entire amino acid chains of A1 and A5 is close to 97%.…”

Efficacy of a Potential Trivalent Vaccine Based on Hc Fragments of Botulinum Toxins A, B, and E Produced in a Cell-Free Expression System

“…Extensive study was devoted in the past decade to develop second generation botulinum vaccines that are based on recombinant nontoxic fragments of the neurotoxin (47,52). The 50-kDa carboxy terminal of the neurotoxin heavy chain (Hc) was found to carry most of the neutralizing epitopes (58) and is the leading candidate for recombinant botulinum vac- (5). However, expression of recombinant Hc proteins in these systems met some major challenges, including the demand for laborious synthetic gene generation and difficulties in purifying the recombinant protein as a soluble secreted product (38,41).…”

Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background

“…A recent review of the antigenic determinants of PA has shown a dearth of information on B-cell epitopes (50). In this regard, the peptide reactivity study provided additional information on the linear B-cell epitopes recognized by immune sera and previously generated MAbs.…”