Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses
Open accessAbstract
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 (ID 50) 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.
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Nucleoside-modified mRNA-LNP vaccines encoding the SARS-CoV-2 spike protein can elicit SARS-CoV-1 and batCoV cross-neutralizing antibodies.
“Saunders and colleagues212 have shown that nucleoside-modified mRNA–LNP vaccines encoding the SARS-CoV-2 spike protein can elicit SARS-CoV-1 and batCoV cross-neutralizing antibodies.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [212]
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mRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · see citing works
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In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms
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Moore, K. A., Leighton, T., Ostrowsky, J. T., Anderson, C. J., Danila, R. N., Ulrich, A. K., Lackritz, E. M., Mehr, A. J., Baric, R. S., Baylor, N. W., et al. (2023) · Vaccine · doi:10.1016/j.vaccine.2023.02.032 · Cited by 25 · see citing works
Self-citationGatechompol, S., Kittanamongkolchai, W., Ketloy, C., Prompetchara, E., Thitithanyanont, A., Jongkaewwattana, A., Buranapraditkun, S., Alameh, M.-G., Ubolyam, S., Sophonphan, J., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01271-0 · Cited by 15 · see citing works
Self-citation
- Authors
- Saunders, K. O., Lee, E., Parks, R., Martinez, D. R., Li, D., Chen, H., Edwards, R. J., Gobeil, S., Barr, M., Mansouri, K., Alam, S. M., Sutherland, L. L., Cai, F., Sanzone, A. M., Berry, M., Manne, K., Bock, K. W., Minai, M., Nagata, B. M., Kapingidza, A. B., Azoitei, M., Tse, L. V., Scobey, T. D., Spreng, R. L., Rountree, R. W., DeMarco, C. T., Denny, T. N., Woods, C. W., Petzold, E. W., Tang, J., Oguin, T. H., Sempowski, G. D., Gagne, M., Douek, D. C., Tomai, M. A., Fox, C. B., Seder, R., Wiehe, K., Weissman, D., Pardi, N., Golding, H., Khurana, S., Acharya, P., Andersen, H., Lewis, M. G., Moore, I. N., Montefiori, D. C., Baric, R. S., & Haynes, B. F.
- Affiliations
- Duke University (US)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Duke Medical Center (US)
- Center for Biologics Evaluation and Research (US)
- 3M (United States) (US)
- Infectious Disease Research Institute (US)
- University of Pennsylvania (US)
- Bioqual (US)
- Corresponding author
- Saunders, Kevin O.
- Haynes, Barton F.
- ORCID
- 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.
- 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.
- Denny, Thomas N.
- Woods, Christopher W.
- Tang, Juanjie
- Oguin, Thomas H.
- Sempowski, Gregory D.
- 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.
- Venue
- Nature
- Published
- 2021-05-10
- Volume
- 594
- Issue
- 7864
- Pages
- 553-559
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8528238
- OpenAlex
- W3161032756
- Cited by
- 253
- References
- 75
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 32 · 2023: 43 · 2022: 87 · 2021: 50
- FWCI
- 16.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- ImmPort
- Funders
- U.S. Department of Defense
- University of Wisconsin-Madison
- North Carolina General Assembly
- National Institutes of Health (1f32ai152296-01a1, USA-WA1/2020, AI142596, U42OD021458, P40OD012217)
- Centers for Disease Control and Prevention
- Defense Advanced Research Projects Agency (HR0011‐17‐2‐0069)
- University of North Carolina at Chapel Hill
- National Cancer Institute (U54CA260543)
- National Institute of Allergy and Infectious Diseases (R01AI157155, AI152296, F32 AI152296, UC6AI058607, U19AI142596, T32AI007151)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, betacoronaviruses, neutralizing antibodies, nanoparticle vaccine, receptor binding domain, alum adjuvant, SARS-CoV, bat coronaviruses, SARS-CoV-2 variants, pan-coronavirus vaccine, mRNA vaccines, zoonotic coronaviruses
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adjuvants, Immunologic, Administration, Intranasal, Animals, Common Cold, Cross Reactions, Disease Models, Animal, Female, Humans, Macaca, Male, Models, Molecular, Trachea, Vaccination, Viral Vaccines, Nanoparticles, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus
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