title: Discovering neutralizing antibodies targeting the stem epitope of H1N1 influenza hemagglutinin with synthetic phage-displayed antibody libraries.
abstract: Broadly neutralizing antibodies developed from the IGHV1-69 germline gene are known to bind to the stem region of hemagglutinin in diverse influenza viruses but the sequence determinants for the antigen recognition, including neutralization potency and binding affinity, are not clearly understood. Such understanding could inform designs of synthetic antibody libraries targeting the stem epitope on hemagglutinin, leading to artificially designed antibodies that are functionally advantageous over antibodies from natural antibody repertoires. In this work, the sequence space of the complementarity determining regions of a broadly neutralizing antibody (F10) targeting the stem epitope on the hemagglutinin of a strain of H1N1 influenza virus was systematically explored; the elucidated antibody-hemagglutinin recognition principles were used to design a phage-displayed antibody library, which was then used to discover neutralizing antibodies against another strain of H1N1 virus. More than 1000 functional antibody candidates were selected from the antibody library and were shown to neutralize the corresponding strain of influenza virus with up to 7 folds higher potency comparing with the parent F10 antibody. The antibody library could be used to discover functionally effective antibodies against other H1N1 influenza viruses, supporting the notion that target-specific antibody libraries can be designed and constructed with systematic sequence-function information.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Tung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Ing-Chien
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Yu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Hung-Pin
authors.initials: HP
authors.lastname: Peng
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.|Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan 112.|Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Jhih-Wei
authors.initials: JW
authors.lastname: Jian
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Shiou-Hwa
authors.initials: SH
authors.lastname: Ma
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: Jia-Tsrong
authors.initials: JT
authors.lastname: Jan
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan 115.
authors.forename: An-Suei
authors.initials: AS
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D003429:Cross Reactions; D004285:Dogs; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D019151:Peptide Library; D011485:Protein Binding; D057127:Single-Chain Antibodies / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019151:Peptide Library; D057127:Single-Chain Antibodies