Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Panpan Zhou; Ge Song; Hejun Liu; Meng Yuan; Wan ting He; Nathan Beutler; Xueyong Zhu; Longping V. Tse; David R. Martinez; Alexandra Schäfer; Fabio Anzanello; Peter Yong; Linghang Peng; Katharina Dueker; Rami Musharrafieh; Sean Callaghan; Tazio Capozzola; Oliver Limbo; Mara Parren; Elijah Garcia; Stephen A. Rawlings; Davey M. Smith; David Nemazee; Joseph G. Jardine; Yana Safonova; Bryan Briney; Thomas F. Rogers; Ian A. Wilson; Ralph S. Baric; Lisa E. Gralinski; Dennis R. Burton; Raiees Andrabi

doi:10.1016/j.immuni.2023.02.005

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Panpan Zhou, Ge Song, Hejun Liu, Meng Yuan, Wan ting He, Nathan Beutler, Xueyong Zhu, Longping V. Tse, David R. Martinez, Alexandra Schäfer, Fabio Anzanello, Peter Yong, Linghang Peng, Katharina Dueker, Rami Musharrafieh, Sean Callaghan, Tazio Capozzola, Oliver Limbo, Mara Parren, Elijah GarciaStephen A. Rawlings, Davey M. Smith, David Nemazee, Joseph G. Jardine, Yana Safonova, Bryan Briney, Thomas F. Rogers, Ian A. Wilson, Ralph S. Baric, Lisa E. Gralinski, Dennis R. Burton, Raiees Andrabi

Computer Science and Engineering

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

43 Scopus citations

Abstract

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.

Original language	English (US)
Pages (from-to)	669-686.e7
Journal	Immunity
Volume	56
Issue number	3
DOIs	https://doi.org/10.1016/j.immuni.2023.02.005
State	Published - Mar 14 2023

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

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

Access to Document

10.1016/j.immuni.2023.02.005

Cite this

Zhou, P., Song, G., Liu, H., Yuan, M., He, W. T., Beutler, N., Zhu, X., Tse, L. V., Martinez, D. R., Schäfer, A., Anzanello, F., Yong, P., Peng, L., Dueker, K., Musharrafieh, R., Callaghan, S., Capozzola, T., Limbo, O., Parren, M., ... Andrabi, R. (2023). Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease. Immunity, 56(3), 669-686.e7. https://doi.org/10.1016/j.immuni.2023.02.005

@article{bbd501b3a2c2488aa12494765ca467fa,

title = "Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease",

abstract = "Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.",

author = "Panpan Zhou and Ge Song and Hejun Liu and Meng Yuan and He, {Wan ting} and Nathan Beutler and Xueyong Zhu and Tse, {Longping V.} and Martinez, {David R.} and Alexandra Sch{\"a}fer and Fabio Anzanello and Peter Yong and Linghang Peng and Katharina Dueker and Rami Musharrafieh and Sean Callaghan and Tazio Capozzola and Oliver Limbo and Mara Parren and Elijah Garcia and Rawlings, {Stephen A.} and Smith, {Davey M.} and David Nemazee and Jardine, {Joseph G.} and Yana Safonova and Bryan Briney and Rogers, {Thomas F.} and Wilson, {Ian A.} and Baric, {Ralph S.} and Gralinski, {Lisa E.} and Burton, {Dennis R.} and Raiees Andrabi",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = mar,

day = "14",

doi = "10.1016/j.immuni.2023.02.005",

language = "English (US)",

volume = "56",

pages = "669--686.e7",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "3",

}

Zhou, P, Song, G, Liu, H, Yuan, M, He, WT, Beutler, N, Zhu, X, Tse, LV, Martinez, DR, Schäfer, A, Anzanello, F, Yong, P, Peng, L, Dueker, K, Musharrafieh, R, Callaghan, S, Capozzola, T, Limbo, O, Parren, M, Garcia, E, Rawlings, SA, Smith, DM, Nemazee, D, Jardine, JG, Safonova, Y, Briney, B, Rogers, TF, Wilson, IA, Baric, RS, Gralinski, LE, Burton, DR & Andrabi, R 2023, 'Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease', Immunity, vol. 56, no. 3, pp. 669-686.e7. https://doi.org/10.1016/j.immuni.2023.02.005

TY - JOUR

T1 - Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

AU - Zhou, Panpan

AU - Song, Ge

AU - Liu, Hejun

AU - Yuan, Meng

AU - He, Wan ting

AU - Beutler, Nathan

AU - Zhu, Xueyong

AU - Tse, Longping V.

AU - Martinez, David R.

AU - Schäfer, Alexandra

AU - Anzanello, Fabio

AU - Yong, Peter

AU - Peng, Linghang

AU - Dueker, Katharina

AU - Musharrafieh, Rami

AU - Callaghan, Sean

AU - Capozzola, Tazio

AU - Limbo, Oliver

AU - Parren, Mara

AU - Garcia, Elijah

AU - Rawlings, Stephen A.

AU - Smith, Davey M.

AU - Nemazee, David

AU - Jardine, Joseph G.

AU - Safonova, Yana

AU - Briney, Bryan

AU - Rogers, Thomas F.

AU - Wilson, Ian A.

AU - Baric, Ralph S.

AU - Gralinski, Lisa E.

AU - Burton, Dennis R.

AU - Andrabi, Raiees

PY - 2023/3/14

Y1 - 2023/3/14

N2 - Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.

AB - Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.

UR - http://www.scopus.com/inward/record.url?scp=85149959411&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85149959411&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2023.02.005

DO - 10.1016/j.immuni.2023.02.005

M3 - Article

C2 - 36889306

AN - SCOPUS:85149959411

SN - 1074-7613

VL - 56

SP - 669-686.e7

JO - Immunity

JF - Immunity

IS - 3

ER -

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Cite this