Systematic analysis of human antibody response to ebolavirus glycoprotein shows high prevalence of neutralizing public clonotypes
Elaine C. Chen,
Pavlo Gilchuk,
Seth J. Zost,
Philipp A. Ilinykh,
Elad Binshtein,
Kai Huang,
Luke Myers,
Stefano Bonissone,
Samuel Day,
Chandrahaas R. Kona,
Andrew Trivette,
Joseph X. Reidy,
Rachel E. Sutton,
Christopher Gainza,
Summer Diaz,
Jazmean K. Williams,
Christopher N. Selverian,
Edgar Davidson,
Erica Ollmann Saphire,
Benjamin J. Doranz,
Natalie Castellana,
Alexander Bukreyev,
Robert H. Carnahan,
James E. Crowe, Jr.
Affiliations
Elaine C. Chen
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Pavlo Gilchuk
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Seth J. Zost
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Philipp A. Ilinykh
Galveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
Elad Binshtein
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Kai Huang
Galveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
Luke Myers
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Stefano Bonissone
Abterra Biosciences, San Diego, CA 92109, USA
Samuel Day
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Chandrahaas R. Kona
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Andrew Trivette
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Joseph X. Reidy
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Rachel E. Sutton
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Christopher Gainza
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Summer Diaz
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Jazmean K. Williams
Integral Molecular, Inc., Philadelphia, PA 19104, USA
Christopher N. Selverian
Integral Molecular, Inc., Philadelphia, PA 19104, USA
Edgar Davidson
Integral Molecular, Inc., Philadelphia, PA 19104, USA
Erica Ollmann Saphire
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Benjamin J. Doranz
Integral Molecular, Inc., Philadelphia, PA 19104, USA
Natalie Castellana
Abterra Biosciences, San Diego, CA 92109, USA
Alexander Bukreyev
Galveston National Laboratory, Galveston, TX 77550, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Robert H. Carnahan
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
James E. Crowe, Jr.
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Corresponding author
Summary: Understanding the human antibody response to emerging viral pathogens is key to epidemic preparedness. As the size of the B cell response to a pathogenic-virus-protective antigen is poorly defined, we perform deep paired heavy- and light-chain sequencing in Ebola virus glycoprotein (EBOV-GP)-specific memory B cells, allowing analysis of the ebolavirus-specific antibody repertoire both genetically and functionally. This approach facilitates investigation of the molecular and genetic basis for the evolution of cross-reactive antibodies by elucidating germline-encoded properties of antibodies to EBOV and identification of the overlap between antibodies in the memory B cell and serum repertoire. We identify 73 public clonotypes of EBOV, 20% of which encode antibodies with neutralization activity and capacity to protect mice in vivo. This comprehensive analysis of the public and private antibody repertoire provides insight into the molecular basis of the humoral immune response to EBOV GP, which informs the design of vaccines and improved therapeutics.
