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

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

doi:10.1016/j.immuni.2023.02.005

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

Journal Article · Thu Feb 16 00:00:00 UTC 2023 · Immunity

DOI: https://doi.org/10.1016/j.immuni.2023.02.005 · OSTI ID:2423303

Zhou, Panpan ^[1]; Song, Ge ^[1]; Liu, Hejun ^[1]; Yuan, Meng ^[1]; He, Wan-ting ^[1]; Beutler, Nathan ^[1]; Zhu, Xueyong ^[1]; Tse, Longping V. ^[2]; Martinez, David R. ^[2]; Schäfer, Alexandra ^[2]; Anzanello, Fabio ^[1]; Yong, Peter ^[1]; Peng, Linghang ^[1]; Dueker, Katharina ^[1]; Musharrafieh, Rami ^[1]; Callaghan, Sean ^[1]; Capozzola, Tazio ^[1]; Limbo, Oliver ^[1]; Parren, Mara ^[1]; Garcia, Elijah ^[1] more »

The Scripps Research Inst., La Jolla, CA (United States)
Univ. of North Carolina, Chapel Hill, NC (United States)
Univ. of California, San Diego, CA (United States)
Johns Hopkins Univ., Baltimore, MD (United States)
The Scripps Research Inst., La Jolla, CA (United States); Univ. of California, San Diego, CA (United States)
The Scripps Research Inst., La Jolla, CA (United States); Harvard Univ., Cambridge, MA (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357; AC02-76SF00515

OSTI ID:: 2423303

Journal Information:: Immunity, Journal Name: Immunity Journal Issue: 3 Vol. 56; ISSN 1074-7613

Publisher:: Cell PressCopyright Statement

Country of Publication:: United States

Language:: English

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A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates Joyce, M. Gordon; King, Hannah A. D.; Elakhal-Naouar, Ines Science Translational Medicine, Vol. 14, Issue 632 https://doi.org/10.1126/scitranslmed.abi5735	journal	February 2022
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Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection Greaney, Allison J.; Loes, Andrea N.; Gentles, Lauren E. Science Translational Medicine, Vol. 13, Issue 600 https://doi.org/10.1126/scitranslmed.abi9915	journal	June 2021
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