Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models.

Autor: Cohen AA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., van Doremalen N; Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., Greaney AJ; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.; Department of Genome Sciences and Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA., Andersen H; BIOQUAL, Rockville, MD, USA., Sharma A; BIOQUAL, Rockville, MD, USA., Starr TN; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.; Department of Genome Sciences and Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA., Keeffe JR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Fan C; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Schulz JE; Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., Gnanapragasam PNP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Kakutani LM; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., West AP Jr; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Saturday G; Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., Lee YE; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Gao H; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Jette CA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Lewis MG; BIOQUAL, Rockville, MD, USA., Tan TK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK., Townsend AR; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.; Chinese Academy of Medical Sciences, Oxford Institute, University of Oxford, Oxford OX3 9DS, UK., Bloom JD; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.; Howard Hughes Medical Institute, Seattle, WA 98109, USA., Munster VJ; Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Aug 05; Vol. 377 (6606), pp. eabq0839. Date of Electronic Publication: 2022 Aug 05.
DOI: 10.1126/science.abq0839
Abstrakt: To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.
Databáze: MEDLINE
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