Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine

Peter J Halfmann; Kathryn Loeffler; Augustine Duffy; Makoto Kuroda; Jie E Yang; Elizabeth R Wright; Yoshihiro Kawaoka; Ravi S Kane

doi:10.1038/s41467-024-45495-6

Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine

Nat Commun. 2024 Feb 12;15(1):1284. doi: 10.1038/s41467-024-45495-6.

Authors

Peter J Halfmann^#¹, Kathryn Loeffler^#², Augustine Duffy^#², Makoto Kuroda¹, Jie E Yang^{3

4

5}, Elizabeth R Wright^{3

4

5}, Yoshihiro Kawaoka^{6

7

8

9}, Ravi S Kane^{10

11}

Affiliations

¹ Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA.
² School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
³ Department of Biochemistry, University of Wisconsin, Madison, WI, 53706, USA.
⁴ Department of Biochemistry, Cryo-EM Research Center, University of Wisconsin, Madison, WI, 53706, USA.
⁵ Department of Biochemistry, Midwest Center for Cryo-Electron Tomography, University of Wisconsin, Madison, WI, 53706, USA.
⁶ Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin, Madison, WI, 53711, USA. yoshihiro.kawaoka@wisc.edu.
⁷ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan. yoshihiro.kawaoka@wisc.edu.
⁸ The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, 162-8655, Japan. yoshihiro.kawaoka@wisc.edu.
⁹ Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo, 162-8655, Japan. yoshihiro.kawaoka@wisc.edu.
¹⁰ School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA. ravi.kane@chbe.gatech.edu.
¹¹ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA. ravi.kane@chbe.gatech.edu.

^# Contributed equally.

Abstract

The 2002 SARS outbreak, the 2019 emergence of COVID-19, and the continuing evolution of immune-evading SARS-CoV-2 variants together highlight the need for a broadly protective vaccine against ACE2-utilizing sarbecoviruses. While updated variant-matched formulations are a step in the right direction, protection needs to extend beyond SARS-CoV-2 and its variants to include SARS-like viruses. Here, we introduce bivalent and trivalent vaccine formulations using our spike protein nanoparticle platform that completely protect female hamsters against BA.5 and XBB.1 challenges with no detectable virus in the lungs. The trivalent cocktails elicit highly neutralizing responses against all tested Omicron variants and the bat sarbecoviruses SHC014 and WIV1. Finally, our 614D/SHC014/XBB trivalent spike formulation completely protects human ACE2-transgenic female hamsters against challenges with WIV1 and SHC014 with no detectable virus in the lungs. Collectively, these results illustrate that our trivalent protein-nanoparticle cocktail can provide broad protection against SARS-CoV-2-like and SARS-CoV-1-like sarbecoviruses.

MeSH terms

Angiotensin-Converting Enzyme 2
Animals
Antibodies, Neutralizing
Antibodies, Viral
Cricetinae
Female
Humans
Immunization
Nanovaccines*
Severe acute respiratory syndrome-related coronavirus*
Vaccination

Substances

Nanovaccines
Angiotensin-Converting Enzyme 2
Antibodies, Neutralizing
Antibodies, Viral

Grants and funding

P01 AI165077/AI/NIAID NIH HHS/United States