Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Saunders, Kevin O

Lee, Esther

Parks, Robert

Martinez, David R

Li, Dapeng

Chen, Haiyan

Edwards, Robert J

Gobeil, Sophie

Barr, Maggie

Mansouri, Katayoun

Alam, S Munir

Sutherland, Laura L

Cai, Fangping

Sanzone, Aja M

Berry, Madison

Manne, Kartik

Bock, Kevin W

Minai, Mahnaz

Nagata, Bianca M

Kapingidza, Anyway B

Azoitei, Mihai

Tse, Longping V

Scobey, Trevor D

Spreng, Rachel L

Rountree, R Wes

DeMarco, C Todd

Denny, Thomas N

Woods, Christopher W

Petzold, Elizabeth W

Tang, Juanjie

Oguin, Thomas H

Sempowski, Gregory D

Gagne, Matthew

Douek, Daniel C

Tomai, Mark A

Fox, Christopher B

Seder, Robert

Wiehe, Kevin

Weissman, Drew

Pardi, Norbert

Golding, Hana

Khurana, Surender

Acharya, Priyamvada

Andersen, Hanne

Lewis, Mark G

Moore, Ian N

Montefiori, David C

Baric, Ralph S

Haynes, Barton F

2022-05-03T19:01:48Z

2022-05-03T19:01:48Z

2021-06

2022-05-03T19:01:47Z

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)^1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID₅₀) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

10.1038/s41586-021-03594-0

0028-0836

1476-4687

https://hdl.handle.net/10161/25005

eng

Springer Science and Business Media LLC

Nature

10.1038/s41586-021-03594-0

Trachea

Animals

Macaca

Humans

Common Cold

Disease Models, Animal

Viral Vaccines

Adjuvants, Immunologic

Vaccination

Administration, Intranasal

Cross Reactions

Models, Molecular

Female

Male

Nanoparticles

Antibodies, Neutralizing

Pandemics

Spike Glycoprotein, Coronavirus

Betacoronavirus

COVID-19

SARS-CoV-2

COVID-19 Vaccines

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Journal article

Saunders, Kevin O|0000-0001-7399-7954

Li, Dapeng|0000-0002-8131-5914

Gobeil, Sophie|0000-0002-0057-2477

Alam, S Munir|0000-0003-0941-0703

Woods, Christopher W|0000-0001-7240-2453

Sempowski, Gregory D|0000-0003-0391-6594

Montefiori, David C|0000-0003-0856-6319

553

559

7864

Duke

School of Medicine

Staff

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Biochemistry

Immunology

Molecular Genetics and Microbiology

Medicine

Pathology

Surgery

Medicine, Duke Human Vaccine Institute

Medicine, Infectious Diseases

Surgery, Surgical Sciences

Duke Cancer Institute

Duke Human Vaccine Institute

Institutes and Provost's Academic Units

University Institutes and Centers

Duke Global Health Institute

Published

594