Broad neutralization of SARS-related viruses by human monoclonal antibodies

Anna Z. Wec; Daniel Wrapp; Andrew S. Herbert; Daniel P. Maurer; Denise Haslwanter; Mrunal Sakharkar; Rohit K. Jangra; M. Eugenia Dieterle; Asparouh Lilov; Deli Huang; Longping V. Tse; Nicole V. Johnson; Ching Lin Hsieh; Nianshuang Wang; Juergen H. Nett; Elizabeth Champney; Irina Burnina; Michael Brown; Shu Lin; Melanie Sinclair; Carl Johnson; Sarat Pudi; Robert Bortz; Ariel S. Wirchnianski; Ethan Laudermilch; Catalina Florez; J. Maximilian Fels; Cecilia M. O'Brien; Barney S. Graham; David Nemazee; Dennis R. Burton; Ralph S. Baric; James E. Voss; Kartik Chandran; John M. Dye; Jason S. McLellan; Laura M. Walker

doi:10.1126/science.abc7424

Broad neutralization of SARS-related viruses by human monoclonal antibodies

Anna Z. Wec, Daniel Wrapp, Andrew S. Herbert, Daniel P. Maurer, Denise Haslwanter, Mrunal Sakharkar, Rohit K. Jangra, M. Eugenia Dieterle, Asparouh Lilov, Deli Huang, Longping V. Tse, Nicole V. Johnson, Ching Lin Hsieh, Nianshuang Wang, Juergen H. Nett, Elizabeth Champney, Irina Burnina, Michael Brown, Shu Lin, Melanie SinclairCarl Johnson, Sarat Pudi, Robert Bortz, Ariel S. Wirchnianski, Ethan Laudermilch, Catalina Florez, J. Maximilian Fels, Cecilia M. O'Brien, Barney S. Graham, David Nemazee, Dennis R. Burton, Ralph S. Baric, James E. Voss, Kartik Chandran, John M. Dye, Jason S. McLellan, Laura M. Walker

Microbiology & Immunology

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

382 Scopus citations

Abstract

Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.

Original language	English (US)
Pages (from-to)	731-736
Number of pages	6
Journal	Science
Volume	369
Issue number	6504
DOIs	https://doi.org/10.1126/science.abc7424
State	Published - Aug 7 2020

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UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Wec, A. Z., Wrapp, D., Herbert, A. S., Maurer, D. P., Haslwanter, D., Sakharkar, M., Jangra, R. K., Eugenia Dieterle, M., Lilov, A., Huang, D., Tse, L. V., Johnson, N. V., Hsieh, C. L., Wang, N., Nett, J. H., Champney, E., Burnina, I., Brown, M., Lin, S., ... Walker, L. M. (2020). Broad neutralization of SARS-related viruses by human monoclonal antibodies. Science, 369(6504), 731-736. https://doi.org/10.1126/science.abc7424

Wec, AZ, Wrapp, D, Herbert, AS, Maurer, DP, Haslwanter, D, Sakharkar, M, Jangra, RK, Eugenia Dieterle, M, Lilov, A, Huang, D, Tse, LV, Johnson, NV, Hsieh, CL, Wang, N, Nett, JH, Champney, E, Burnina, I, Brown, M, Lin, S, Sinclair, M, Johnson, C, Pudi, S, Bortz, R, Wirchnianski, AS, Laudermilch, E, Florez, C, Maximilian Fels, J, O'Brien, CM, Graham, BS, Nemazee, D, Burton, DR, Baric, RS, Voss, JE, Chandran, K, Dye, JM, McLellan, JS & Walker, LM 2020, 'Broad neutralization of SARS-related viruses by human monoclonal antibodies', Science, vol. 369, no. 6504, pp. 731-736. https://doi.org/10.1126/science.abc7424

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abstract = "Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.",

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AU - Jangra, Rohit K.

AU - Eugenia Dieterle, M.

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AU - Hsieh, Ching Lin

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AU - Maximilian Fels, J.

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AU - Graham, Barney S.

AU - Nemazee, David

AU - Burton, Dennis R.

AU - Baric, Ralph S.

AU - Voss, James E.

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AU - Dye, John M.

AU - McLellan, Jason S.

AU - Walker, Laura M.

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Broad neutralization of SARS-related viruses by human monoclonal antibodies

Abstract

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