Designed mosaic nanoparticles enhance cross-reactive immune responses in mice
Summary Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naïve and COVID-19 pre-vaccinated mice revealed that mosaic-7COMelicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COMtargeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COMelicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COMelicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COMto protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 01. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Eric [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.02.28.582544 |
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| PPN (Katalog-ID): |
XBI042675952 |
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| 520 | |a Summary Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naïve and COVID-19 pre-vaccinated mice revealed that mosaic-7COMelicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COMtargeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COMelicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COMelicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COMto protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential. | ||
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| 700 | 1 | |a Keeffe, Jennifer R. |4 aut | |
| 700 | 1 | |a Rorick, Annie V. |4 aut | |
| 700 | 1 | |a Aida, Yusuf M. |4 aut | |
| 700 | 1 | |a Gnanapragasam, Priyanthi N.P. |4 aut | |
| 700 | 1 | |a Bjorkman, Pamela J. |4 aut | |
| 700 | 1 | |a Chakraborty, Arup K. |4 aut | |
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