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

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

doi:10.1101/2022.03.04.479488

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

bioRxiv [Preprint]. 2022 Mar 7:2022.03.04.479488. doi: 10.1101/2022.03.04.479488.

Authors

Panpan Zhou^{1

2

3}, Ge Song^{1

2

3}, Wan-Ting He^{1

2

3}, Nathan Beutler¹, Longping V Tse⁴, David R Martinez⁴, Alexandra Schäfer⁴, Fabio Anzanello^{1

2

3}, Peter Yong^{1

2

3}, Linghang Peng¹, Katharina Dueker^{1

2

3}, Rami Musharrafieh^{1

2

3}, Sean Callaghan^{1

2

3}, Tazio Capozzola^{1

2

3}, Meng Yuan⁵, Hejun Liu⁵, Oliver Limbo², Mara Parren¹, Elijah Garcia¹, Stephen A Rawlings⁶, Davey M Smith⁶, David Nemazee¹, Joseph G Jardine², Ian A Wilson^{2

3

5

7}, Yana Safonova⁸, Thomas F Rogers^{1

6}, Ralph S Baric^{4

9}, Lisa E Gralinski⁴, Dennis R Burton^{1

2

3

10}, Raiees Andrabi^{1

2

3}

Affiliations

¹ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
² IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
³ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁶ Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
⁷ Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁸ Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA.
⁹ Departments of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁰ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.

Abstract

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against coronaviruses that cause severe disease, for anticipating novel pandemic-causing viruses, and to respond more effectively to SARS-CoV-2 variants. The emergence of the Omicron variant of SARS-CoV-2 has illustrated the limitations of solely targeting the receptor binding domain (RBD) of the envelope Spike (S)-protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors that target a conserved S2 region in the fusion machinery on betacoronavirus spikes. Select bnAbs show broad in vivo protection against all three pathogenic betacoronaviruses, SARS-CoV-1, SARS-CoV-2 and MERS-CoV, that have spilled over into humans in the past 20 years to cause severe disease. The bnAbs provide new opportunities for antibody-based interventions and key insights for developing pan-betacoronavirus vaccines.

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Preprint

Abstract

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