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

Research output: Contribution to journalArticlepeer-review

25 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 languageEnglish (US)
Pages (from-to)669-686.e7
JournalImmunity
Volume56
Issue number3
DOIs
StatePublished - Mar 14 2023

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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