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Title: Structural and molecular basis for Ebola virus neutralization by protective human antibodies

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1249224
Resource Type:
Journal Article
Resource Relation:
Journal Name: Science; Journal Volume: 351; Journal Issue: 6279
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Misasi, J., Gilman, M. S. A., Kanekiyo, M., Gui, M., Cagigi, A., Mulangu, S., Corti, D., Ledgerwood, J. E., Lanzavecchia, A., Cunningham, J., Muyembe-Tamfun, J. J., Baxa, U., Graham, B. S., Xiang, Y., Sullivan, N. J., and McLellan, J. S. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. United States: N. p., 2016. Web. doi:10.1126/science.aad6117.
Misasi, J., Gilman, M. S. A., Kanekiyo, M., Gui, M., Cagigi, A., Mulangu, S., Corti, D., Ledgerwood, J. E., Lanzavecchia, A., Cunningham, J., Muyembe-Tamfun, J. J., Baxa, U., Graham, B. S., Xiang, Y., Sullivan, N. J., & McLellan, J. S. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. United States. doi:10.1126/science.aad6117.
Misasi, J., Gilman, M. S. A., Kanekiyo, M., Gui, M., Cagigi, A., Mulangu, S., Corti, D., Ledgerwood, J. E., Lanzavecchia, A., Cunningham, J., Muyembe-Tamfun, J. J., Baxa, U., Graham, B. S., Xiang, Y., Sullivan, N. J., and McLellan, J. S. 2016. "Structural and molecular basis for Ebola virus neutralization by protective human antibodies". United States. doi:10.1126/science.aad6117.
@article{osti_1249224,
title = {Structural and molecular basis for Ebola virus neutralization by protective human antibodies},
author = {Misasi, J. and Gilman, M. S. A. and Kanekiyo, M. and Gui, M. and Cagigi, A. and Mulangu, S. and Corti, D. and Ledgerwood, J. E. and Lanzavecchia, A. and Cunningham, J. and Muyembe-Tamfun, J. J. and Baxa, U. and Graham, B. S. and Xiang, Y. and Sullivan, N. J. and McLellan, J. S.},
abstractNote = {},
doi = {10.1126/science.aad6117},
journal = {Science},
number = 6279,
volume = 351,
place = {United States},
year = 2016,
month = 7
}
  • We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/{delta}F-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/{delta}F-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface,more » the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/{delta}F-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.« less
  • Cited by 26
  • The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of theirmore » NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. We find that these structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry.« less
    Cited by 26
  • The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of theirmore » NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. We find that these structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry.« less