Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

Dapeng Li; David R Martinez; Alexandra Schäfer; Haiyan Chen; Maggie Barr; Laura L Sutherland; Esther Lee; Robert Parks; Dieter Mielke; Whitney Edwards; Amanda Newman; Kevin W Bock; Mahnaz Minai; Bianca M Nagata; Matthew Gagne; Daniel C Douek; C Todd DeMarco; Thomas N Denny; Thomas H Oguin 3rd; Alecia Brown; Wes Rountree; Yunfei Wang; Katayoun Mansouri; Robert J Edwards; Guido Ferrari; Gregory D Sempowski; Amanda Eaton; Juanjie Tang; Derek W Cain; Sampa Santra; Norbert Pardi; Drew Weissman; Mark A Tomai; Christopher B Fox; Ian N Moore; Hanne Andersen; Mark G Lewis; Hana Golding; Robert Seder; Surender Khurana; Ralph S Baric; David C Montefiori; Kevin O Saunders; Barton F Haynes

doi:10.1038/s41467-022-33985-4

Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

Nat Commun. 2022 Oct 23;13(1):6309. doi: 10.1038/s41467-022-33985-4.

Authors

Dapeng Li^{1

2}, David R Martinez³, Alexandra Schäfer³, Haiyan Chen^{1

2}, Maggie Barr¹, Laura L Sutherland¹, Esther Lee^{1

2}, Robert Parks¹, Dieter Mielke⁴, Whitney Edwards¹, Amanda Newman^{1

2}, Kevin W Bock⁵, Mahnaz Minai⁵, Bianca M Nagata⁵, Matthew Gagne⁶, Daniel C Douek⁶, C Todd DeMarco^{1

2}, Thomas N Denny^{1

2}, Thomas H Oguin 3rd^{1

2}, Alecia Brown^{1

2}, Wes Rountree^{1

2}, Yunfei Wang^{1

2}, Katayoun Mansouri¹, Robert J Edwards^{1

2}, Guido Ferrari^{1

4}, Gregory D Sempowski^{1

2}, Amanda Eaton^{1

4}, Juanjie Tang⁷, Derek W Cain^{1

2}, Sampa Santra⁸, Norbert Pardi⁹, Drew Weissman¹⁰, Mark A Tomai¹¹, Christopher B Fox¹², Ian N Moore⁵, Hanne Andersen¹³, Mark G Lewis¹³, Hana Golding⁷, Robert Seder⁶, Surender Khurana⁷, Ralph S Baric³, David C Montefiori^{1

4}, Kevin O Saunders^{14

15

16

17}, Barton F Haynes^{18

19

20}

Affiliations

¹ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA.
² Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁴ Department of Surgery, Duke University School of Medicine, Durham, NC, 27710, USA.
⁵ Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20814, USA.
⁶ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20814, USA.
⁷ Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Silver Spring, MD, 20871, USA.
⁸ Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
⁹ Department of Microbiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹⁰ Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹¹ Corporate Research Materials Lab, 3M Company, St Paul, MN, 55144, USA.
¹² Infectious Disease Research Institute, Seattle, WA, 98104, USA.
¹³ BIOQUAL, Rockville, MD, 20850, USA.
¹⁴ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA. kevin.saunders@duke.edu.
¹⁵ Department of Surgery, Duke University School of Medicine, Durham, NC, 27710, USA. kevin.saunders@duke.edu.
¹⁶ Department of Immunology, Duke University School of Medicine, Durham, NC, 27710, USA. kevin.saunders@duke.edu.
¹⁷ Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, 27710, USA. kevin.saunders@duke.edu.
¹⁸ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA. barton.haynes@duke.edu.
¹⁹ Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA. barton.haynes@duke.edu.
²⁰ Department of Immunology, Duke University School of Medicine, Durham, NC, 27710, USA. barton.haynes@duke.edu.

Abstract

Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / chemistry
Antibodies, Viral
COVID-19* / prevention & control
Ferritins
Mice
Mice, Inbred BALB C
Nanoparticles*
SARS-CoV-2 / genetics
Severe acute respiratory syndrome-related coronavirus*
Spike Glycoprotein, Coronavirus
Viral Vaccines*

Substances

Spike Glycoprotein, Coronavirus
Antibodies, Viral
Antibodies, Neutralizing
Viral Vaccines
Ferritins
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

P51 OD011132/OD/NIH HHS/United States