Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

Kang Wang; Binyang Zheng; Li Zhang; Lunbiao Cui; Xuan Su; Qian Zhang; Zhenxi Guo; Yu Guo; Wei Zhang; Ling Zhu; Fengcai Zhu; Zihe Rao; Xiangxi Wang

doi:10.1038/s41467-020-18250-w

Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

Kang Wang, Binyang Zheng, Li Zhang, Lunbiao Cui, Xuan Su, Qian Zhang, Zhenxi Guo, Yu Guo, Wei Zhang, Ling Zhu, Fengcai Zhu, Zihe Rao, Xiangxi Wang

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

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Abstract

Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.

Original language	English (US)
Article number	4419
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18250-w
State	Published - Dec 1 2020
Externally published	Yes

Bibliographical note

Funding Information:
We thank B. Zhu, X. Huang and G. Ji for Cryo-EM data collection at the Center for Biological imaging (CBI), Institute of Biophysics, and X. Pei for sample screening and data collection in the cryo-EM platform of PKU. We also thank Y. Chen, Z. Yang and B. Zhou for SPR technical support and X. Yu for AUC technical guidance. Work was supported by the Strategic Priority Research Program (XDB29010000), Beijing Natural Science Foundation-Haidian Primitive Innovation Joint fund (19L2008), the Key Programs of the Chinese Academy (KJZD-SW-L05), the National Key Research and Development Program (2018YFA0900801 and 2017YFC0840300), National Science Foundation of China (31800145, 31941011, 31900873 and 81520108019) and Center for Biosafety Mega-Science, CAS and Applied Technology Research and Development Project of Heilongjiang Province (GA19B301). Xiangxi Wang was supported by Ten Thousand Talent Program and the NSFS Innovative Research Group (No. 81921005). Ling Zhu was supported by the Youth Innovation Promotion Association at the Chinese Academy of Sciences (2019098).

Publisher Copyright:
© 2020, The Author(s).

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

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@article{57ceb167513d41f48ef84f314c6a0e64,

title = "Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B",

abstract = "Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.",

author = "Kang Wang and Binyang Zheng and Li Zhang and Lunbiao Cui and Xuan Su and Qian Zhang and Zhenxi Guo and Yu Guo and Wei Zhang and Ling Zhu and Fengcai Zhu and Zihe Rao and Xiangxi Wang",

note = "Funding Information: We thank B. Zhu, X. Huang and G. Ji for Cryo-EM data collection at the Center for Biological imaging (CBI), Institute of Biophysics, and X. Pei for sample screening and data collection in the cryo-EM platform of PKU. We also thank Y. Chen, Z. Yang and B. Zhou for SPR technical support and X. Yu for AUC technical guidance. Work was supported by the Strategic Priority Research Program (XDB29010000), Beijing Natural Science Foundation-Haidian Primitive Innovation Joint fund (19L2008), the Key Programs of the Chinese Academy (KJZD-SW-L05), the National Key Research and Development Program (2018YFA0900801 and 2017YFC0840300), National Science Foundation of China (31800145, 31941011, 31900873 and 81520108019) and Center for Biosafety Mega-Science, CAS and Applied Technology Research and Development Project of Heilongjiang Province (GA19B301). Xiangxi Wang was supported by Ten Thousand Talent Program and the NSFS Innovative Research Group (No. 81921005). Ling Zhu was supported by the Youth Innovation Promotion Association at the Chinese Academy of Sciences (2019098). Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

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doi = "10.1038/s41467-020-18250-w",

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T1 - Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

AU - Wang, Kang

AU - Zheng, Binyang

AU - Zhang, Li

AU - Cui, Lunbiao

AU - Su, Xuan

AU - Zhang, Qian

AU - Guo, Zhenxi

AU - Guo, Yu

AU - Zhang, Wei

AU - Zhu, Ling

AU - Zhu, Fengcai

AU - Rao, Zihe

AU - Wang, Xiangxi

N1 - Funding Information: We thank B. Zhu, X. Huang and G. Ji for Cryo-EM data collection at the Center for Biological imaging (CBI), Institute of Biophysics, and X. Pei for sample screening and data collection in the cryo-EM platform of PKU. We also thank Y. Chen, Z. Yang and B. Zhou for SPR technical support and X. Yu for AUC technical guidance. Work was supported by the Strategic Priority Research Program (XDB29010000), Beijing Natural Science Foundation-Haidian Primitive Innovation Joint fund (19L2008), the Key Programs of the Chinese Academy (KJZD-SW-L05), the National Key Research and Development Program (2018YFA0900801 and 2017YFC0840300), National Science Foundation of China (31800145, 31941011, 31900873 and 81520108019) and Center for Biosafety Mega-Science, CAS and Applied Technology Research and Development Project of Heilongjiang Province (GA19B301). Xiangxi Wang was supported by Ten Thousand Talent Program and the NSFS Innovative Research Group (No. 81921005). Ling Zhu was supported by the Youth Innovation Promotion Association at the Chinese Academy of Sciences (2019098). Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.

AB - Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.

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Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

Abstract

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