Enhanced humanization and affinity maturation of neutralizing anti-hepatitis B virus preS1 antibody based on antigen-antibody complex structure

Title
Enhanced humanization and affinity maturation of neutralizing anti-hepatitis B virus preS1 antibody based on antigen-antibody complex structure
Authors
류성언
Keywords
Humanized antibody; Specificity-determining residue grafting; Affinity maturation; Hepatitis B virus; preS1; Virus neutralization
Issue Date
2015-01
Publisher
ELSEVIER SCIENCE BV
Citation
FEBS LETTERS, v. 589, NO 2, Page. 193-200
Abstract
To improve a previously constructed broadly neutralizing hepatitis B virus (HBV)-specific preS1 humanized antibody (HzKR127), we further humanized it through specificity-determining residue (SDR) grafting. Moreover, we improved affinity by mutating two residues in heavy-chain complementarity-determining regions (CDR), on the basis of the crystal structure of the antigen-antibody complex. HzKR127-3.2 exhibited 2.5-fold higher affinity and enhanced virus-neutralizing activity compared to the original KR127 antibody and showed less immunogenic potential than HzKR127. Enhanced virus-neutralizing activity was achieved by the increased association rate, providing insights into engineering potent antibody therapeutics for HBV immunoprophylaxis. HzKR127-3.2 may be a good candidate for HBV immunoprophylaxis. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/20.500.11754/21306http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2014.11.046/abstract?systemMessage=Pay+Per+View+on+Wiley+Online+Library+will+be+unavailable+on+Saturday+15th+April+from+12%3A00-09%3A00+EDT+for+essential+maintenance.++Apologies+for+the+inconvenience.
ISSN
0014-5793
DOI
http://dx.doi.org/10.1016/j.febslet.2014.11.046
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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