Bacillus anthracis

About: Bacillus anthracis is a research topic. Over the lifetime, 3994 publications have been published within this topic receiving 128122 citations.

Selection of a Macaque Fab with Framework Regions Like Those in Humans, High Affinity, and Ability To Neutralize the Protective Antigen (PA) of Bacillus anthracis by Binding to the Segment of PA between Residues 686 and 694

Abstract: Human anthrax infection cannot always be treated successfully by antibiotics, as highlighted by recent bioterrorist attacks; thus, adjunct therapies are clearly needed for the future. There is a particular need to further develop adjunct therapies that can neutralize secreted toxins, such as antibodies directed towards the 83-kDa protective antigen (PA 83 ). In the absence of human donors, we immunized a macaque ( Macaca fascicularis ) with PA 83 to obtain such antibodies suitable as an adjunct therapy for human anthrax infection. By using bone marrow as a template, we PCR amplified specific Fab-encoding genes and cloned them as an immune library (10 7 clones). We isolated a high-affinity (equilibrium dissociation constant [ K D ], 3.4 nM), highly neutralizing (50% inhibitory concentration, 5.6 ± 0.13 nM) Fab (designated 35PA 83 ) from this library by panning. Its epitope was localized by Pepscan analysis between residues 686 and 694 of PA 83 and is part of the region which directly interacts with the cell receptor. 35PA 83 may thus neutralize the anthrax toxin by competing directly for its receptor. The genes encoding 35PA 83 were similar to those of a human immunoglobulin germ line and were assigned to subgroups of human V, (D), or J genes by IMGT/V-QUEST analysis. The 35PA 83 framework regions were 92% identical to a representative allele of each subgroup. When compared to framework regions coded by related human germ line genes, only 2 of 74 (VH) or 75 (VK) analyzed amino acids of 35PA 83 have different chemical characteristics. A very high degree of identity with human framework regions makes 35PA 83 well suited for expression as a whole primatized immunoglobulin G and demonstrates the practicality of using macaque Fabs when immunized human plasma cell donors are not available.

Safety, reactogenicity and immunogenicity of a recombinant protective antigen anthrax vaccine given to healthy adults.

Abstract: BACKGROUND: Bacillus anthracis causes anthrax, a vaccine-preventable zoonotic disease that may follow intentional or unintentional exposure to its spores. Although an anthrax vaccine is currently licensed in the USA, better vaccines are desirable for both pre- and post-exposure prophylaxis.METHODS: Healthy adults, aged 18 to 40 years, received anthrax immunization with either licensed Anthrax Vaccine Adsorbed (AVA, BioThrax™), or an experimental recombinant Protective Antigen vaccine (rPA) produced from an avirulent, non-spore-forming strain of B. anthracis at one of 4 doses (5, 25, 50, or 75 μg). Volunteers were followed for safety, reactogenicity, and immunogenicity.RESULTS: rPA vaccine was well tolerated with a low rate of local or systemic reactions. Although antibody responses were poor following unadjuvanted rPA administration, 89 and 100% of volunteers who received Alhydrogel-adjuvanted rPA given intramuscularly had 4-fold increases by enzyme-linked immunosorbent and toxin neutralization assays, re...