Epitopes described in "Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody."

Article Authors:A Nowakowski; C Wang; D B Powers; P Amersdorfer; T J Smith; V A Montgomery; R Sheridan; R Blake; L A Smith; J D Marks
Article Title:Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody.
Reference Detail
Reference ID:1001647
Abstract:The botulinum neurotoxins (BoNTs) cause the paralytic human disease botulism and are one of the highest-risk threat agents for bioterrorism. To generate a pharmaceutical to prevent or treat botulism, monoclonal antibodies (mAbs) were generated by phage display and evaluated for neutralization of BoNT serotype A (BoNT/A) in vivo. Although no single mAb significantly neutralized toxin, a combination of three mAbs (oligoclonal Ab) neutralized 450,000 50% lethal doses of BoNT/A, a potency 90 times greater than human hyperimmune globulin. The potency of oligoclonal Ab was primarily due to a large increase in functional Ab binding affinity. The results indicate that the potency of the polyclonal humoral immune response can be deconvoluted to a few mAbs binding nonoverlapping epitopes, providing a route to drugs for preventing and treating botulism and diseases caused by other pathogens and biologic threat agents.
Affiliations:Department of Anesthesia and Pharmaceutical Chemistry, University of California, Room 3C-38, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Reference Type:Literature
PubMed ID:12177434
Journal:Proc Natl Acad Sci U S A
Journal Volume:99
Article Pages:11346-50
Journal ISSN:0027-8424
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6bfaa41;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@114294dd;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2a3b4205;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@186b6bec;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@347a5f7a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4e125d80;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@17b8a68b
Article MeSH List:Animals; Antibodies, Bacterial(immunology); Antibodies, Monoclonal(immunology); Antibody Specificity; Base Sequence; Botulinum Toxins(immunology); DNA Primers; Immunoglobulin G(immunology); Immunoglobulin Heavy Chains(genetics; immunology); Kinetics; Male; Mice; Neutralization Tests; Phrenic Nerve(immunology); Polymerase Chain Reaction; Recombinant Proteins(immunology); Time Factors
Curation Last Updated:2015-01-17 21:10:40