The DOI matches its Crossref record; 116 of the 116 references it cites were found in a registry or an index.
Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines
Open accessPublished version of a preprint
Abstract
Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies. We benchmarked NHP serum neutralizing activity elicited by RBD-NP against a lead prefusion-stabilized SARS-CoV-2 spike immunogen using a panel of single-residue spike mutants detected in clinical isolates as well as the B.1.1.7 and B.1.351 variants of concern. Polyclonal antibodies elicited by both vaccines are resilient to most RBD mutations tested, but the E484K substitution has similar negative consequences for neutralization, and exhibit modest but comparable neutralization breadth against distantly related sarbecoviruses. We demonstrate that mosaic and cocktail sarbecovirus RBD-NPs elicit broad sarbecovirus neutralizing activity, including against the SARS-CoV-2 B.1.351 variant, and protect mice against severe SARS-CoV challenge even in the absence of the SARS-CoV RBD in the vaccine. This study provides proof of principle that sarbecovirus RBD-NPs induce heterotypic protection and enables advancement of broadly protective sarbecovirus vaccines to the clinic.
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“For example, prototypes of multivalent nanoparticle vaccines have been reported to induce broad reactivity against different sarbecoviruses7.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [7]
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Result
Metadata
- Authors
- Walls, A. C., Miranda, M. C., Schäfer, A., Pham, M. N., Greaney, A., Arunachalam, P. S., Navarro, M.-J., Tortorici, M. A., Rogers, K., O’Connor, M. A., Shirreff, L., Ferrell, D. E., Bowen, J., Brunette, N., Kepl, E., Zepeda, S. K., Starr, T., Hsieh, C.-L., Fiala, B., Wrenn, S., Pettie, D., Sydeman, C., Sprouse, K. R., Johnson, M., Blackstone, A., Ravichandran, R., Ogohara, C., Carter, L., Tilles, S. W., Rappuoli, R., Leist, S. R., Martinez, D. R., Clark, M., Tisch, R., O’Hagan, D. T., Van Der Most, R., Van Voorhis, W. C., Corti, D., McLellan, J. S., Kleanthous, H., Sheahan, T. P., Smith, K. D., Fuller, D. H., Villinger, F., Bloom, J., Pulendran, B., Baric, R. S., King, N. P., & Veesler, D.
- Affiliations
- University of Washington (US)
- University of North Carolina at Chapel Hill (US)
- Stanford University (US)
- Centre National de la Recherche Scientifique (FR)
- University of Louisiana at Lafayette (US)
- Fred Hutch Cancer Center (US)
- The University of Texas at Austin (US)
- GlaxoSmithKline (Italy) (IT)
- Vir Biotechnology (Switzerland) (CH)
- Gates Foundation (US)
- Corresponding author
- King, Neil P.
- Veesler, David
- ORCID
- Walls, Alexandra C.
- Miranda, Marcos C.
- Schäfer, Alexandra
- Pham, Minh N.
- Greaney, Allison
- Arunachalam, Prabhu S.
- Navarro, Mary-Jane
- Tortorici, M. Alejandra
- Rogers, Kenneth
- O’Connor, Megan A.
- Shirreff, Lisa
- Ferrell, Douglas E.
- Bowen, John
- Brunette, Natalie
- Kepl, Elizabeth
- Zepeda, Samantha K.
- Starr, Tyler
- Hsieh, Ching-Lin
- Fiala, Brooke
- Wrenn, Samuel
- Pettie, Deleah
- Sprouse, Kaitlin R.
- Johnson, Max
- Ravichandran, Rashmi
- Carter, Lauren
- Tilles, Sasha W.
- Rappuoli, Rino
- Leist, Sarah R.
- Martinez, David R.
- Clark, Matthew
- Tisch, Roland
- Corti, Davide
- McLellan, Jason S.
- Kleanthous, Harry
- Sheahan, Timothy P.
- Smith, Kelly D.
- Fuller, Deborah H.
- Villinger, Francois
- Bloom, Jesse
- Pulendran, Bali
- Baric, Ralph S.
- King, Neil P.
- Veesler, David
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 184
- Issue
- 21
- Pages
- 5432-5447.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7986998
- OpenAlex
- W3199882158
- Cited by
- 185
- References
- 116
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 27 · 2023: 35 · 2022: 59 · 2021: 25
- FWCI
- 11.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- Burroughs Wellcome Fund (U01 AI149644, HHSN272201700036I-75N93020F00001)
- Howard Hughes Medical Institute
- Defense Threat Reduction Agency (HDTRA1-18-1-0001)
- National Institute of General Medical Sciences (R01GM120553)
- Bill and Melinda Gates Foundation (017592, OPP1156262, INV\u2013017592)
- Pfizer
- University of Washington
- Gilead Sciences
- GlaxoSmithKline (63/032,502)
- North Carolina General Assembly
- National Institute of Allergy and Infectious Diseases (DP1AI158186, F32 AI152296, T32 AI007151, R01-AI127521, 5T32GM008268-32, HHSN272201700059C)
- Office of Research Infrastructure Programs, National Institutes of Health (P51-OD010425)
- 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
- Sarbecovirus, SARS-CoV-2, receptor binding domain, nanoparticle vaccine, multivalent vaccine, heterologous protection, neutralizing antibodies, SARS-CoV, spike protein mutations, mosaic vaccine, dose sparing, non-human primates
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