Designed mosaic nanoparticles enhance cross-reactive immune responses in mice

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Acknowledgement

This work was supported by the National Science Foundation Graduate Research Fellowship: 1745302 (E.W.), the National Institutes of Health: 1-R61-AI161805-01 and U19AI057229 (A.K.C.), the National Institutes of Health: P01-AI165075 (P.J.B.), Wellcome Leap (P.J.B.), Bill and Melinda Gates Foundation: INV-034638 (P.J.B.), the Coalition for Epidemic Preparedness Innovations (CEPI) (P.J.B.), and the Merkin Institute for Translational Research (Caltech). E.W. and A.K.C. acknowledge the MIT SuperCloud and Lincoln Laboratory Supercomputing Center for providing HPC resources that have contributed to the research results reported within this work.

We thank Jesse Bloom (Fred Hutchinson), Allie Greaney (University of Washington), and Tyler Starr (University of Utah) for RBD libraries and help setting up DMS at Caltech, Noor Youssef (Harvard Medical School) and Ziyan Wu (Caltech) for radar plot Python scripts, Jost Vielmetter, Luisa Segovia, Annie Lam, and the Caltech Beckman Institute Protein Expression Center for protein production, Igor Antoshechkin and the Caltech Millard and Muriel Jacobs Genetics and Genomics Laboratory for Illumina sequencing, Chengcheng Fan for generating RBD-NP models, Labcorp Drug Development (Denver, PA) for performing mouse immunizations, and Anthony West for calculating the probabilities of identical neighboring RBDs.

Contributions

Conceptualization: E.W, A.K.C., A.A.C., P.J.B.; Methodology: E.W, A.K.C. (computations); J.R.K., A.V.R., Y.M.A., P.N.P.G. (experiments); Computation and Software: E.W., A.K.C.; Investigation: E.W. (computations); J.R.K., A.V.R., Y.M.A., P.N.P.G. (experiments); Writing – original draft: E.W., A.K.C, A.A.C, L.F.C., P.J.B.; Writing – review and editing: E.W., A.K.C, A.A.C, L.F.C., P.J.B.; Visualization: E.W., A.A.C, L.F.C.; Supervision: A.K.C, P.J.B.; Project Administration: A.K.C., P.J.B.; Funding: A.K.C., P.J.B.

Conflict of Interest

A.K.C. is a consultant (titled “Academic Partner”) for Flagship Pioneering, consultant and Strategic Oversight Board Member of its affiliated company, Apriori Bio, and is a consultant and Scientific Advisory Board Member of another affiliated company, Metaphore Bio.

P.J.B. and A.A.C. are inventors on a US patent application (17/523,813) filed by the California Institute of Technology that covers mosaic RBD-NPs. P.J.B. is a scientific advisor for Vaccine Company, Inc. and for Vir Biotechnology.