Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

M. Alejandra Tortorici; Martina Beltramello; Florian A. Lempp; Dora Pinto; Ha V. Dang; Laura E. Rosen; Matthew McCallum; John Bowen; Andrea Minola; Stefano Jaconi; Fabrizia Zatta; Anna De Marco; Barbara Guarino; Siro Bianchi; Elvin J. Lauron; Heather Tucker; Jiayi Zhou; Alessia Peter; Colin Havenar-Daughton; Jason A. Wojcechowskyj; James Brett Case; Rita E. Chen; Hannah Kaiser; Martin Montiel-Ruiz; Marcel Meury; Nadine Czudnochowski; Roberto Spreafico; Josh Dillen; Cindy Ng; Nicole Sprugasci; Katja Culap; Fabio Benigni; Rana Abdelnabi; Shi Yan Caroline Foo; Michael A. Schmid; Elisabetta Cameroni; Agostino Riva; Arianna Gabrieli; Massimo Galli; Matteo S. Pizzuto; Johan Neyts; Michael S. Diamond; Herbert W. Virgin; Gyorgy Snell; Davide Corti; Katja Fink; David Veesler

doi:10.1126/science.abe3354

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

M. Alejandra Tortorici, Martina Beltramello, Florian A. Lempp, Dora Pinto, Ha V. Dang, Laura E. Rosen, Matthew McCallum, John Bowen, Andrea Minola, Stefano Jaconi, Fabrizia Zatta, Anna De Marco, Barbara Guarino, Siro Bianchi, Elvin J. Lauron, Heather Tucker, Jiayi Zhou, Alessia Peter, Colin Havenar-Daughton, Jason A. WojcechowskyjJames Brett Case, Rita E. Chen, Hannah Kaiser, Martin Montiel-Ruiz, Marcel Meury, Nadine Czudnochowski, Roberto Spreafico, Josh Dillen, Cindy Ng, Nicole Sprugasci, Katja Culap, Fabio Benigni, Rana Abdelnabi, Shi Yan Caroline Foo, Michael A. Schmid, Elisabetta Cameroni, Agostino Riva, Arianna Gabrieli, Massimo Galli, Matteo S. Pizzuto, Johan Neyts, Michael S. Diamond, Herbert W. Virgin, Gyorgy Snell, Davide Corti, Katja Fink, David Veesler

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

278 Scopus citations

Abstract

Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.

Original language	English
Pages (from-to)	950-957
Number of pages	8
Journal	Science
Volume	370
Issue number	6519
DOIs	https://doi.org/10.1126/science.abe3354
State	Published - Nov 20 2020

Access to Document

10.1126/science.abe3354

Cite this

Tortorici, M. A., Beltramello, M., Lempp, F. A., Pinto, D., Dang, H. V., Rosen, L. E., McCallum, M., Bowen, J., Minola, A., Jaconi, S., Zatta, F., De Marco, A., Guarino, B., Bianchi, S., Lauron, E. J., Tucker, H., Zhou, J., Peter, A., Havenar-Daughton, C., ... Veesler, D. (2020). Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. Science, 370(6519), 950-957. https://doi.org/10.1126/science.abe3354

@article{6faea8a4e0254307a7381a4684aa5864,

title = "Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms",

abstract = "Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.",

author = "Tortorici, {M. Alejandra} and Martina Beltramello and Lempp, {Florian A.} and Dora Pinto and Dang, {Ha V.} and Rosen, {Laura E.} and Matthew McCallum and John Bowen and Andrea Minola and Stefano Jaconi and Fabrizia Zatta and {De Marco}, Anna and Barbara Guarino and Siro Bianchi and Lauron, {Elvin J.} and Heather Tucker and Jiayi Zhou and Alessia Peter and Colin Havenar-Daughton and Wojcechowskyj, {Jason A.} and Case, {James Brett} and Chen, {Rita E.} and Hannah Kaiser and Martin Montiel-Ruiz and Marcel Meury and Nadine Czudnochowski and Roberto Spreafico and Josh Dillen and Cindy Ng and Nicole Sprugasci and Katja Culap and Fabio Benigni and Rana Abdelnabi and Foo, {Shi Yan Caroline} and Schmid, {Michael A.} and Elisabetta Cameroni and Agostino Riva and Arianna Gabrieli and Massimo Galli and Pizzuto, {Matteo S.} and Johan Neyts and Diamond, {Michael S.} and Virgin, {Herbert W.} and Gyorgy Snell and Davide Corti and Katja Fink and David Veesler",

year = "2020",

month = nov,

day = "20",

doi = "10.1126/science.abe3354",

language = "English",

volume = "370",

pages = "950--957",

journal = "Science",

issn = "0036-8075",

number = "6519",

}

Tortorici, MA, Beltramello, M, Lempp, FA, Pinto, D, Dang, HV, Rosen, LE, McCallum, M, Bowen, J, Minola, A, Jaconi, S, Zatta, F, De Marco, A, Guarino, B, Bianchi, S, Lauron, EJ, Tucker, H, Zhou, J, Peter, A, Havenar-Daughton, C, Wojcechowskyj, JA, Case, JB, Chen, RE, Kaiser, H, Montiel-Ruiz, M, Meury, M, Czudnochowski, N, Spreafico, R, Dillen, J, Ng, C, Sprugasci, N, Culap, K, Benigni, F, Abdelnabi, R, Foo, SYC, Schmid, MA, Cameroni, E, Riva, A, Gabrieli, A, Galli, M, Pizzuto, MS, Neyts, J, Diamond, MS, Virgin, HW, Snell, G, Corti, D, Fink, K & Veesler, D 2020, 'Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms', Science, vol. 370, no. 6519, pp. 950-957. https://doi.org/10.1126/science.abe3354

TY - JOUR

T1 - Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

AU - Tortorici, M. Alejandra

AU - Beltramello, Martina

AU - Lempp, Florian A.

AU - Pinto, Dora

AU - Dang, Ha V.

AU - Rosen, Laura E.

AU - McCallum, Matthew

AU - Bowen, John

AU - Minola, Andrea

AU - Jaconi, Stefano

AU - Zatta, Fabrizia

AU - De Marco, Anna

AU - Guarino, Barbara

AU - Bianchi, Siro

AU - Lauron, Elvin J.

AU - Tucker, Heather

AU - Zhou, Jiayi

AU - Peter, Alessia

AU - Havenar-Daughton, Colin

AU - Wojcechowskyj, Jason A.

AU - Case, James Brett

AU - Chen, Rita E.

AU - Kaiser, Hannah

AU - Montiel-Ruiz, Martin

AU - Meury, Marcel

AU - Czudnochowski, Nadine

AU - Spreafico, Roberto

AU - Dillen, Josh

AU - Ng, Cindy

AU - Sprugasci, Nicole

AU - Culap, Katja

AU - Benigni, Fabio

AU - Abdelnabi, Rana

AU - Foo, Shi Yan Caroline

AU - Schmid, Michael A.

AU - Cameroni, Elisabetta

AU - Riva, Agostino

AU - Gabrieli, Arianna

AU - Galli, Massimo

AU - Pizzuto, Matteo S.

AU - Neyts, Johan

AU - Diamond, Michael S.

AU - Virgin, Herbert W.

AU - Snell, Gyorgy

AU - Corti, Davide

AU - Fink, Katja

AU - Veesler, David

PY - 2020/11/20

Y1 - 2020/11/20

N2 - Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.

AB - Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.

UR - http://www.scopus.com/inward/record.url?scp=85096508515&partnerID=8YFLogxK

U2 - 10.1126/science.abe3354

DO - 10.1126/science.abe3354

M3 - Article

C2 - 32972994

AN - SCOPUS:85096508515

VL - 370

SP - 950

EP - 957

JO - Science

JF - Science

SN - 0036-8075

IS - 6519

ER -

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

Abstract

Access to Document

Other files and links

Fingerprint

Cite this