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

doi:10.1016/j.celrep.2023.112370

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. DoranzNatalie Castellana, Alexander Bukreyev, Robert H. Carnahan, James E. Crowe

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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.

Original language	English (US)
Article number	112370
Journal	Cell Reports
Volume	42
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2023.112370
State	Published - Apr 25 2023
Externally published	Yes

Keywords

CP: Immunology
Ebola
adaptive immunity
antibodies
human
monoclonal
repertoire

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2023.112370

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Chen, E. C., Gilchuk, P., Zost, S. J., Ilinykh, P. A., Binshtein, E., Huang, K., Myers, L., Bonissone, S., Day, S., Kona, C. R., Trivette, A., Reidy, J. X., Sutton, R. E., Gainza, C., Diaz, S., Williams, J. K., Selverian, C. N., Davidson, E., Saphire, E. O., ... Crowe, J. E. (2023). Systematic analysis of human antibody response to ebolavirus glycoprotein shows high prevalence of neutralizing public clonotypes. Cell Reports, 42(4), Article 112370. https://doi.org/10.1016/j.celrep.2023.112370

Chen, EC, Gilchuk, P, Zost, SJ, Ilinykh, PA, Binshtein, E, Huang, K, Myers, L, Bonissone, S, Day, S, Kona, CR, Trivette, A, Reidy, JX, Sutton, RE, Gainza, C, Diaz, S, Williams, JK, Selverian, CN, Davidson, E, Saphire, EO, Doranz, BJ, Castellana, N, Bukreyev, A, Carnahan, RH & Crowe, JE 2023, 'Systematic analysis of human antibody response to ebolavirus glycoprotein shows high prevalence of neutralizing public clonotypes', Cell Reports, vol. 42, no. 4, 112370. https://doi.org/10.1016/j.celrep.2023.112370

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abstract = "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.",

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author = "Chen, {Elaine C.} and Pavlo Gilchuk and Zost, {Seth J.} and Ilinykh, {Philipp A.} and Elad Binshtein and Kai Huang and Luke Myers and Stefano Bonissone and Samuel Day and Kona, {Chandrahaas R.} and Andrew Trivette and Reidy, {Joseph X.} and Sutton, {Rachel E.} and Christopher Gainza and Summer Diaz and Williams, {Jazmean K.} and Selverian, {Christopher N.} and Edgar Davidson and Saphire, {Erica Ollmann} and Doranz, {Benjamin J.} and Natalie Castellana and Alexander Bukreyev and Carnahan, {Robert H.} and Crowe, {James E.}",

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doi = "10.1016/j.celrep.2023.112370",

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AU - Chen, Elaine C.

AU - Gilchuk, Pavlo

AU - Zost, Seth J.

AU - Ilinykh, Philipp A.

AU - Binshtein, Elad

AU - Huang, Kai

AU - Myers, Luke

AU - Bonissone, Stefano

AU - Day, Samuel

AU - Kona, Chandrahaas R.

AU - Trivette, Andrew

AU - Reidy, Joseph X.

AU - Sutton, Rachel E.

AU - Gainza, Christopher

AU - Diaz, Summer

AU - Williams, Jazmean K.

AU - Selverian, Christopher N.

AU - Davidson, Edgar

AU - Saphire, Erica Ollmann

AU - Doranz, Benjamin J.

AU - Castellana, Natalie

AU - Bukreyev, Alexander

AU - Carnahan, Robert H.

AU - Crowe, James E.

PY - 2023/4/25

Y1 - 2023/4/25

N2 - 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.

AB - 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.

KW - CP: Immunology

KW - Ebola

KW - adaptive immunity

KW - antibodies

KW - human

KW - monoclonal

KW - repertoire

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Systematic analysis of human antibody response to ebolavirus glycoprotein shows high prevalence of neutralizing public clonotypes

Abstract

Keywords

ASJC Scopus subject areas

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