title: Enhanced humanization and affinity maturation of neutralizing anti-hepatitis B virus preS1 antibody based on antigen-antibody complex structure.
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.
authors.affiliation: Institute of Antibody Research, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Jin Hong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Institut de Recherche Santé Environnement et Travail (IRSET) - U.1085, Institut National de la Santé et de la Recherche Médicale (Inserm), Rennes, Bretagne, France; Université de Rennes 1, Rennes, Bretagne, France; Structure Fédérative Biosit UMS 3480 CNRS-US18 Inserm, Rennes, Bretagne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gripon
authors.affiliation: Institut de Recherche Santé Environnement et Travail (IRSET) - U.1085, Institut National de la Santé et de la Recherche Médicale (Inserm), Rennes, Bretagne, France; Université de Rennes 1, Rennes, Bretagne, France; Structure Fédérative Biosit UMS 3480 CNRS-US18 Inserm, Rennes, Bretagne, France.
authors.forename: Fidaa
authors.initials: F
authors.lastname: Bouezzedine
authors.affiliation: Institute of Antibody Research, Kangwon National University, Chuncheon 200-701, Republic of Korea; Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Mun Sik
authors.initials: MS
authors.lastname: Jeong
authors.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Chi
authors.affiliation: Department of Bio-engineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Seong-Eon
authors.initials: SE
authors.lastname: Ryu
authors.affiliation: Institute of Antibody Research, Kangwon National University, Chuncheon 200-701, Republic of Korea; Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: hjhong@kangwon.ac.kr.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Hong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000936:Antigen-Antibody Complex; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D018984:Epitopes, T-Lymphocyte; D006510:Hepatitis B Antibodies; D014764:Viral Proteins
keywords: Affinity maturation; Hepatitis B virus; Humanized antibody; Specificity-determining residue grafting; Virus neutralization; preS1