Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization

Pavlo Gilchuk; Charles D. Murin; Jacob C. Milligan; Robert W. Cross; Chad E. Mire; Philipp A. Ilinykh; Kai Huang; Natalia Kuzmina; Pilar X. Altman; Sean Hui; Bronwyn M. Gunn; Aubrey L. Bryan; Edgar Davidson; Benjamin J. Doranz; Hannah L. Turner; Tanwee Alkutkar; Robin Flinko; Chiara Orlandi; Robert Carnahan; Rachel Nargi; Robin G. Bombardi; Megan E. Vodzak; Sheng Li; Adaora Okoli; Morris Ibeawuchi; Benjamin Ohiaeri; George K. Lewis; Galit Alter; Alexander Bukreyev; Erica Ollmann Saphire; Thomas W. Geisbert; Andrew B. Ward; James E. Crowe

doi:10.1016/j.immuni.2020.01.001

Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization

Pavlo Gilchuk
, Charles D. Murin
, Jacob C. Milligan
, Robert W. Cross
, Chad E. Mire
, Philipp A. Ilinykh
, Kai Huang
, Natalia Kuzmina
, Pilar X. Altman
, Sean Hui
, Bronwyn M. Gunn
, Aubrey L. Bryan
, Edgar Davidson
, Benjamin J. Doranz
, Hannah L. Turner
, Tanwee Alkutkar
, Robin Flinko
, Chiara Orlandi
, Robert Carnahan
, Rachel Nargi

Robin G. Bombardi, Megan E. Vodzak, Sheng Li, Adaora Okoli, Morris Ibeawuchi, Benjamin Ohiaeri, George K. Lewis, Galit Alter, Alexander Bukreyev, Erica Ollmann Saphire, Thomas W. Geisbert, Andrew B. Ward, James E. Crowe

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

68 Scopus citations

Abstract

Cooperative interactions of monoclonal antibodies (mAbs) with viral antigens are poorly understood. Gilchuk et al. perform structural and functional analysis of cooperativity in a cocktail of two human mAbs, recognizing major epitopes of ebolavirus glycoprotein (GP), and define cooperative binding of the GP as a mechanism for enhanced ebolavirus neutralization.

Original language	English (US)
Pages (from-to)	388-403.e12
Journal	Immunity
Volume	52
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2020.01.001
State	Published - Feb 18 2020

Keywords

Ebolavirus
antibody synergy
antibody therapeutics
cooperative neutralization
ebolavirus infection
epitope mapping
glycoprotein
molecular mimicry
neutralizing antibodies
viral antibodies

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2020.01.001

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Gilchuk, P., Murin, C. D., Milligan, J. C., Cross, R. W., Mire, C. E., Ilinykh, P. A., Huang, K., Kuzmina, N., Altman, P. X., Hui, S., Gunn, B. M., Bryan, A. L., Davidson, E., Doranz, B. J., Turner, H. L., Alkutkar, T., Flinko, R., Orlandi, C., Carnahan, R., ... Crowe, J. E. (2020). Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization. Immunity, 52(2), 388-403.e12. https://doi.org/10.1016/j.immuni.2020.01.001

Gilchuk, P, Murin, CD, Milligan, JC, Cross, RW, Mire, CE, Ilinykh, PA, Huang, K, Kuzmina, N, Altman, PX, Hui, S, Gunn, BM, Bryan, AL, Davidson, E, Doranz, BJ, Turner, HL, Alkutkar, T, Flinko, R, Orlandi, C, Carnahan, R, Nargi, R, Bombardi, RG, Vodzak, ME, Li, S, Okoli, A, Ibeawuchi, M, Ohiaeri, B, Lewis, GK, Alter, G, Bukreyev, A, Saphire, EO, Geisbert, TW, Ward, AB & Crowe, JE 2020, 'Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization', Immunity, vol. 52, no. 2, pp. 388-403.e12. https://doi.org/10.1016/j.immuni.2020.01.001

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title = "Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization",

abstract = "Cooperative interactions of monoclonal antibodies (mAbs) with viral antigens are poorly understood. Gilchuk et al. perform structural and functional analysis of cooperativity in a cocktail of two human mAbs, recognizing major epitopes of ebolavirus glycoprotein (GP), and define cooperative binding of the GP as a mechanism for enhanced ebolavirus neutralization.",

keywords = "Ebolavirus, antibody synergy, antibody therapeutics, cooperative neutralization, ebolavirus infection, epitope mapping, glycoprotein, molecular mimicry, neutralizing antibodies, viral antibodies",

author = "Pavlo Gilchuk and Murin, \{Charles D.\} and Milligan, \{Jacob C.\} and Cross, \{Robert W.\} and Mire, \{Chad E.\} and Ilinykh, \{Philipp A.\} and Kai Huang and Natalia Kuzmina and Altman, \{Pilar X.\} and Sean Hui and Gunn, \{Bronwyn M.\} and Bryan, \{Aubrey L.\} and Edgar Davidson and Doranz, \{Benjamin J.\} and Turner, \{Hannah L.\} and Tanwee Alkutkar and Robin Flinko and Chiara Orlandi and Robert Carnahan and Rachel Nargi and Bombardi, \{Robin G.\} and Vodzak, \{Megan E.\} and Sheng Li and Adaora Okoli and Morris Ibeawuchi and Benjamin Ohiaeri and Lewis, \{George K.\} and Galit Alter and Alexander Bukreyev and Saphire, \{Erica Ollmann\} and Geisbert, \{Thomas W.\} and Ward, \{Andrew B.\} and Crowe, \{James E.\}",

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year = "2020",

month = feb,

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doi = "10.1016/j.immuni.2020.01.001",

language = "English (US)",

volume = "52",

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AU - Murin, Charles D.

AU - Milligan, Jacob C.

AU - Cross, Robert W.

AU - Mire, Chad E.

AU - Ilinykh, Philipp A.

AU - Huang, Kai

AU - Kuzmina, Natalia

AU - Altman, Pilar X.

AU - Hui, Sean

AU - Gunn, Bronwyn M.

AU - Bryan, Aubrey L.

AU - Davidson, Edgar

AU - Doranz, Benjamin J.

AU - Turner, Hannah L.

AU - Alkutkar, Tanwee

AU - Flinko, Robin

AU - Orlandi, Chiara

AU - Carnahan, Robert

AU - Nargi, Rachel

AU - Bombardi, Robin G.

AU - Vodzak, Megan E.

AU - Li, Sheng

AU - Okoli, Adaora

AU - Ibeawuchi, Morris

AU - Ohiaeri, Benjamin

AU - Lewis, George K.

AU - Alter, Galit

AU - Bukreyev, Alexander

AU - Saphire, Erica Ollmann

AU - Geisbert, Thomas W.

AU - Ward, Andrew B.

AU - Crowe, James E.

PY - 2020/2/18

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AB - Cooperative interactions of monoclonal antibodies (mAbs) with viral antigens are poorly understood. Gilchuk et al. perform structural and functional analysis of cooperativity in a cocktail of two human mAbs, recognizing major epitopes of ebolavirus glycoprotein (GP), and define cooperative binding of the GP as a mechanism for enhanced ebolavirus neutralization.

KW - Ebolavirus

KW - antibody synergy

KW - antibody therapeutics

KW - cooperative neutralization

KW - ebolavirus infection

KW - epitope mapping

KW - glycoprotein

KW - molecular mimicry

KW - neutralizing antibodies

KW - viral antibodies

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AN - SCOPUS:85079145867

SN - 1074-7613

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JO - Immunity

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Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization

Abstract

Keywords

ASJC Scopus subject areas

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