Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody

Jason S. McLellan; Man Chen; Sherman Leung; Kevin W. Graepel; Xiulian Du; Yongping Yang; Tongqing Zhou; Ulrich Baxa; Etsuko Yasuda; Tim Beaumont; Azad Kumar; Kayvon Modjarrad; Zizheng Zheng; Min Zhao; Ningshao Xia; Peter D. Kwong; Barney S. Graham

doi:https://doi.org/10.1126/science.1234914

Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody

Jason S. McLellan, Man Chen, Sherman Leung, Kevin W. Graepel, Xiulian Du, Yongping Yang, Tongqing Zhou, Ulrich Baxa, Etsuko Yasuda, Tim Beaumont, Azad Kumar, Kayvon Modjarrad, Zizheng Zheng, Min Zhao, Ningshao Xia, Peter D. Kwong, Barney S. Graham

Amsterdam UMC

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

589 Citations (Scopus)

Abstract

The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease

Original language	English
Pages (from-to)	1113-1117
Journal	Science
Volume	340
Issue number	6136
DOIs	https://doi.org/10.1126/science.1234914
Publication status	Published - 2013

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https://doi.org/10.1126/science.1234914

Cite this

McLellan, J. S., Chen, M., Leung, S., Graepel, K. W., Du, X., Yang, Y., Zhou, T., Baxa, U., Yasuda, E., Beaumont, T., Kumar, A., Modjarrad, K., Zheng, Z., Zhao, M., Xia, N., Kwong, P. D., & Graham, B. S. (2013). Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science, 340(6136), 1113-1117. https://doi.org/10.1126/science.1234914

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title = "Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody",

abstract = "The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site {\O}. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease",

author = "McLellan, {Jason S.} and Man Chen and Sherman Leung and Graepel, {Kevin W.} and Xiulian Du and Yongping Yang and Tongqing Zhou and Ulrich Baxa and Etsuko Yasuda and Tim Beaumont and Azad Kumar and Kayvon Modjarrad and Zizheng Zheng and Min Zhao and Ningshao Xia and Kwong, {Peter D.} and Graham, {Barney S.}",

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AU - McLellan, Jason S.

AU - Chen, Man

AU - Leung, Sherman

AU - Graepel, Kevin W.

AU - Du, Xiulian

AU - Yang, Yongping

AU - Zhou, Tongqing

AU - Baxa, Ulrich

AU - Yasuda, Etsuko

AU - Beaumont, Tim

AU - Kumar, Azad

AU - Modjarrad, Kayvon

AU - Zheng, Zizheng

AU - Zhao, Min

AU - Xia, Ningshao

AU - Kwong, Peter D.

AU - Graham, Barney S.

PY - 2013

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AB - The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease

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DO - https://doi.org/10.1126/science.1234914

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