Functional interrogation and mining of natively paired human VH:VL antibody repertoires

Bo Wang; Brandon J DeKosky; Morgan R Timm; Jiwon Lee; Erica Normandin; John Misasi; Rui Kong; Jonathan R McDaniel; George Delidakis; Kendra E Leigh; Thomas Niezold; Chang W Choi; Elise G Viox; Ahmed Fahad; Alberto Cagigi; Aurélie Ploquin; Kwanyee Leung; Eun Sung Yang; Wing-Pui Kong; William N Voss; Aaron G Schmidt; M Anthony Moody; David R Ambrozak; Amy R Henry; Farida Laboune; Julie E Ledgerwood; Barney S Graham; Mark Connors; Daniel C Douek; Nancy J Sullivan; Andrew D Ellington; John R Mascola; George Georgiou

doi:10.1038/nbt.4052

Functional interrogation and mining of natively paired human V_H:V_L antibody repertoires

Nat Biotechnol. 2018 Feb;36(2):152-155. doi: 10.1038/nbt.4052. Epub 2018 Jan 8.

Authors

Bo Wang¹, Brandon J DeKosky^{2

3

4}, Morgan R Timm², Jiwon Lee¹, Erica Normandin², John Misasi², Rui Kong², Jonathan R McDaniel¹, George Delidakis¹, Kendra E Leigh², Thomas Niezold², Chang W Choi², Elise G Viox², Ahmed Fahad⁴, Alberto Cagigi², Aurélie Ploquin², Kwanyee Leung², Eun Sung Yang², Wing-Pui Kong², William N Voss¹, Aaron G Schmidt⁵, M Anthony Moody^{6

7}, David R Ambrozak², Amy R Henry², Farida Laboune², Julie E Ledgerwood², Barney S Graham², Mark Connors⁸, Daniel C Douek², Nancy J Sullivan², Andrew D Ellington^{9

10}, John R Mascola², George Georgiou^{1

9

10

11}

Affiliations

¹ Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA.
² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
³ Department of Chemical & Petroleum Engineering, The University of Kansas, Lawrence, Kansas, USA.
⁴ Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas, USA.
⁵ Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA.
⁷ Department of Pediatrics, Duke University Medical School, Durham, North Carolina, USA.
⁸ National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
⁹ Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, USA.
¹⁰ Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA.
¹¹ Department of Bioengineering, The University of Texas at Austin, Austin, Texas, USA.

Abstract

We present a technology to screen millions of B cells for natively paired human antibody repertoires. Libraries of natively paired, variable region heavy and light (V_H:V_L) amplicons are expressed in a yeast display platform that is optimized for human Fab surface expression. Using our method we identify HIV-1 broadly neutralizing antibodies (bNAbs) from an HIV-1 slow progressor and high-affinity neutralizing antibodies against Ebola virus glycoprotein and influenza hemagglutinin.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence / genetics
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / therapeutic use
Antibodies, Neutralizing / immunology*
Antibodies, Neutralizing / therapeutic use
B-Lymphocytes / immunology*
HIV Antibodies / immunology*
HIV Antibodies / therapeutic use
HIV Infections / drug therapy*
HIV Infections / virology
HIV-1 / immunology
HIV-1 / pathogenicity
High-Throughput Nucleotide Sequencing
Humans
Peptide Library

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
HIV Antibodies
Peptide Library

Abstract

Publication types

MeSH terms

Substances

Grants and funding