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Identification and characterization of a neutralizing monoclonal antibody that provides complete protection against Yersinia pestis
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 5, p e0177012 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science, 2017.
-
Abstract
- Yersinia pestis (Y. pestis) has caused an alarming number of deaths throughout recorded human history, and novel prophylactics and therapeutics are necessary given its potential as a bioweapon. Only one monoclonal antibody has been identified to date that provides complete protection against Y. pestis. Here, we describe a second novel murine monoclonal antibody (F2H5) that provided complete protection against Y. pestis 141 infection when administered prophylactically to Balb/c mice (100 μg intravenously). We humanized F2H5, characterized its ability to bind to the Y. pestis F1 protein and further characterized the neutralizing epitope using computational and experimental approaches. While Western blot results suggested a linear epitope, peptide mapping using ELISA failed to identify an epitope, suggesting a conformational epitope instead. We adopted a computational approach based on Residue Contact Frequency to predict the site of antigen-antibody interaction and defined the F2H5/F1 binding site computationally. Based on computational approach, we determined that residues G104E105N106 in F1 were critical to F2H5 binding and that CDRH2 and CDRH3 of F2H5 interacted with F1. Our results show that combining computational approach and experimental approach can effectively identify epitopes.
- Subjects :
- 0301 basic medicine
Proteomics
Physiology
lcsh:Medicine
Pathology and Laboratory Medicine
Atomic Structure
Biochemistry
Epitope
0302 clinical medicine
Immune Physiology
Medicine and Health Sciences
Urea
Enzyme-Linked Immunoassays
lcsh:Science
Multidisciplinary
Immune System Proteins
biology
medicine.diagnostic_test
Organic Compounds
Physics
Chemical Synthesis
Antibodies, Monoclonal
Animal Models
Yersinia
Bacterial Pathogens
Chemistry
Experimental Organism Systems
Medical Microbiology
Physical Sciences
Antibody
Pathogens
Research Article
Yersinia Pestis
Biosynthetic Techniques
medicine.drug_class
Immunology
Mouse Models
Monoclonal antibody
Research and Analysis Methods
Microbiology
Peptide Mapping
Antibodies
03 medical and health sciences
Model Organisms
Western blot
medicine
Humans
Binding site
Immunoassays
Microbial Pathogens
Peptide Synthesis
Linear epitope
Bacteria
lcsh:R
Organic Chemistry
Organisms
Chemical Compounds
Biology and Life Sciences
Proteins
biology.organism_classification
Virology
Antibodies, Neutralizing
Monoclonal Antibodies
030104 developmental biology
Yersinia pestis
Atomic Physics
biology.protein
Immunologic Techniques
lcsh:Q
030215 immunology
Conformational epitope
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c2456d1a823a72802b2fac853fdccb85