Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2–MPER region

Andrew I. Flyak, Natalia Kuzmina, Charles D. Murin, Christopher Bryan, Edgar Davidson, Pavlo Gilchuk, Christopher P. Gulka, Philipp A. Ilinykh, Xiaoli Shen, Kai Huang, Palaniappan Ramanathan, Hannah Turner, Marnie L. Fusco, Rebecca Lampley, Nurgun Kose, Hannah King, Gopal Sapparapu, Benjamin J. Doranz, Thomas Ksiazek, David W. WrightErica Ollmann Saphire, Andrew B. Ward, Alexander Bukreyev, James E. Crowe

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Ebola virus (EBOV) in humans causes a severe illness with high mortality rates. Several strategies have been developed in the past to treat EBOV infection, including the antibody cocktail ZMapp, which has been shown to be effective in nonhuman primate models of infection1 and has been used under compassionate-treatment protocols in humans2. ZMapp is a mixture of three chimerized murine monoclonal antibodies (mAbs)3–6 that target EBOV-specific epitopes on the surface glycoprotein7,8. However, ZMapp mAbs do not neutralize other species from the genus Ebolavirus, such as Bundibugyo virus (BDBV), Reston virus (RESTV) or Sudan virus (SUDV). Here, we describe three naturally occurring human cross-neutralizing mAbs, from BDBV survivors, that target an antigenic site in the canonical heptad repeat 2 (HR2) region near the membrane-proximal external region (MPER) of the glycoprotein. The identification of a conserved neutralizing antigenic site in the glycoprotein suggests that these mAbs could be used to design universal antibody therapeutics against diverse ebolavirus species. Furthermore, we found that immunization with a peptide comprising the HR2–MPER antigenic site elicits neutralizing antibodies in rabbits. Structural features determined by conserved residues in the antigenic site described here could inform an epitope-based vaccine design against infection caused by diverse ebolavirus species.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalNature Microbiology
DOIs
StateAccepted/In press - May 7 2018

Fingerprint

Ebolavirus
Neutralizing Antibodies
Survivors
Glycoproteins
Monoclonal Antibodies
Viruses
Epitopes
Ebola Hemorrhagic Fever
Sudan
Antibodies
Clinical Protocols
Primates
Immunization
Vaccines
Rabbits
Peptides
Membranes
Mortality
Infection
ZMapp

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Cite this

Flyak, A. I., Kuzmina, N., Murin, C. D., Bryan, C., Davidson, E., Gilchuk, P., ... Crowe, J. E. (Accepted/In press). Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2–MPER region. Nature Microbiology, 1-8. https://doi.org/10.1038/s41564-018-0157-z

Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2–MPER region. / Flyak, Andrew I.; Kuzmina, Natalia; Murin, Charles D.; Bryan, Christopher; Davidson, Edgar; Gilchuk, Pavlo; Gulka, Christopher P.; Ilinykh, Philipp A.; Shen, Xiaoli; Huang, Kai; Ramanathan, Palaniappan; Turner, Hannah; Fusco, Marnie L.; Lampley, Rebecca; Kose, Nurgun; King, Hannah; Sapparapu, Gopal; Doranz, Benjamin J.; Ksiazek, Thomas; Wright, David W.; Saphire, Erica Ollmann; Ward, Andrew B.; Bukreyev, Alexander; Crowe, James E.

In: Nature Microbiology, 07.05.2018, p. 1-8.

Research output: Contribution to journalArticle

Flyak, AI, Kuzmina, N, Murin, CD, Bryan, C, Davidson, E, Gilchuk, P, Gulka, CP, Ilinykh, PA, Shen, X, Huang, K, Ramanathan, P, Turner, H, Fusco, ML, Lampley, R, Kose, N, King, H, Sapparapu, G, Doranz, BJ, Ksiazek, T, Wright, DW, Saphire, EO, Ward, AB, Bukreyev, A & Crowe, JE 2018, 'Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2–MPER region', Nature Microbiology, pp. 1-8. https://doi.org/10.1038/s41564-018-0157-z
Flyak, Andrew I. ; Kuzmina, Natalia ; Murin, Charles D. ; Bryan, Christopher ; Davidson, Edgar ; Gilchuk, Pavlo ; Gulka, Christopher P. ; Ilinykh, Philipp A. ; Shen, Xiaoli ; Huang, Kai ; Ramanathan, Palaniappan ; Turner, Hannah ; Fusco, Marnie L. ; Lampley, Rebecca ; Kose, Nurgun ; King, Hannah ; Sapparapu, Gopal ; Doranz, Benjamin J. ; Ksiazek, Thomas ; Wright, David W. ; Saphire, Erica Ollmann ; Ward, Andrew B. ; Bukreyev, Alexander ; Crowe, James E. / Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2–MPER region. In: Nature Microbiology. 2018 ; pp. 1-8.
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