10.1038/nrmicro.2016.81 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 4. from COV7, COV21, Rabbit Polyclonal to RANBP17 and COV72 plasmas ( em 18 /em ) (evaluated at top concentrations of 1500 g/ml) against the indicated strains. Mean = arithmetic mean IC50. Our results confirm that multimerization of RBDs on nanoparticles enhances immunogenicity relative to soluble antigen ( em 33 /em , em 48 /em ). We found that homotypic SARS-2 nanoparticle immunization produces IgG responses that bind zoonotic RBDs and neutralize heterologous coronaviruses after boosting. By contrast, soluble SARS-2 S immunization and natural contamination with SARS-CoV-2 resulted in poor or no heterologous responses in plasmas. Co-display of SARS-2 RBD along with diverse RBDs on mosaic nanoparticles showed no disadvantages for eliciting neutralizing antibodies against SARS-CoV-2 relative to homotypic SARS-2 nanoparticles; therefore, mosaic nanoparticles may represent a candidate vaccine Aloin (Barbaloin) to protect against COVID-19. Furthermore, relative to homotypic SARS-2 RBD particles, the mosaic co-display strategy demonstrated advantages for eliciting Aloin (Barbaloin) neutralizing antibodies against zoonotic sarbecoviruses, thus potentially also providing protection against emerging coronaviruses with human spillover potential. Neutralization of matched and mismatched strains was observed after mosaic priming; hence, a single injection of a mosaic RBD nanoparticle might be sufficient in a vaccine. Because COVID-19 convalescent plasmas showed little to no recognition of coronavirus RBDs other than SARS-CoV-2, COVD-19Cinduced immunity in humans may not protect against another emergent coronavirus. However, the mosaic nanoparticles described here could be used as described or easily adapted Aloin (Barbaloin) so that they present RBDs from newly discovered zoonotic coronaviruses. Acknowledgments We thank K. Brune (Genie Biotech) for guidance about mi3 production; J. Bloom (Fred Hutchinson) and P. Bieniasz (Rockefeller University) for neutralization assay reagents; J. Vielmetter and Caltechs Beckman Institute Protein Expression Center for protein production; A. Flyak for help with flow cytometry; M. Murphy for figures; COVID-19 plasma donors, B. Aloin (Barbaloin) Coller, S. Schlesinger, and the Rockefeller University Hospital Clinical Research Support Office and nursing staff; and A. Flyak and A. DeLaitsch for crucial reading of the manuscript. Funding: Supported by NIH grant P01-AI138938-S1 (P.J.B. and M.C.N.), Aloin (Barbaloin) the Caltech Merkin Institute for Translational Research (P.J.B.), a George Mason University Fast Grant (P.J.B.), and the Medical Research Council (MR/P001351/1) (M.H.) (this UK-funded award is part of the EDCTP2 program supported by the European Union). M.C.N. is usually a Howard Hughes Medical Institute Investigator. Author contributions: A.A.C., C.O.B., and P.J.B. conceived and designed experiments; A.A.C., P.N.P.G., Y.E.L., P.R.H., S.O., and L.M.K. performed experiments; H.-J.W. generated and validated SpyCatcher003-mi3; M.H. supervised the generation and validation of SpyCatcher003-mi3; and A.A.C., J.R.K., A.P.W., C.O.B., M.C.N., and P.J.B. analyzed data and wrote the paper with contributions from other authors. Competing interests: M.H. is an inventor on a patent on SpyTag/SpyCatcher (EP2534484) and a patent application on SpyTag003:SpyCatcher003 (UK Intellectual Property Office 1706430.4), as well as a SpyBiotech cofounder, shareholder, and consultant. P.J.B. and A.A.C. are inventors on a provisional application from the California Institute of Technology that covers the mosaic nanoparticles described in this work. Data and materials availability: All data are available in the main text or the supplementary materials. Materials are available upon request to the corresponding author with a signed material transfer agreement. This work is usually licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material. Supplementary Materials science.sciencemag.org/content/371/6530/735/suppl/DC1 Materials and Methods Figs. S1 to S5 Recommendations ( em 51 /em C em 58 /em ) MDAR Reproducibility Checklist View/request a protocol for this paper from em Bio-protocol /em . References and Notes 1. Zhou P., Yang X.-L., Wang X.-G., Hu B., Zhang L., Zhang W., Si H.-R., Zhu Y., Li B., Huang C.-L., Chen H.-D., Chen J., Luo Y., Guo H., Jiang R.-D., Liu M.-Q., Chen Y., Shen X.-R., Wang X., Zheng X.-S., Zhao K., Chen Q.-J., Deng F., Liu L.-L., Yan B., Zhan F.-X., Wang Y.-Y., Xiao G.-F., Shi Z.-L., A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270C273 (2020). 10.1038/s41586-020-2012-7 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 2. 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