Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses

We thank D. Staunton from the University of Oxford Department of Biochemistry Biophysical Suite for help with biophysical analysis. We thank the Centre for the AIDS Programme of Research in South Africa (CAPRISA) and G. Screaton (University of Oxford) for supplying SARS-CoV-2 variant isolates. The BtKY72 K493Y/T498W Spike plasmid for generating pseudovirus was a kind gift to the Bjorkman lab from D. Veesler (University of Washington). We thank the Cambridge Advanced Imaging Centre for TEM training and access to the microscopy facility. A.H.K. and M.R.H. disclose support for the research of this work from the Biotechnology and Biological Sciences Research Council (BBSRC grant no. BB/S007369/1). M.R.H. discloses support for the research of this work from the University of Oxford COVID-19 Research Response Fund and its donors (reference no. 0009517). R.A.H. discloses support for the research of this work from the Rhodes Trust. T.K.T. discloses support for the research of this work from the EPA Cephalosporin Early Career Teaching and Research Fellowship. R.A.H. and T.K.T. disclose support for the research of this work from the Townsend-Jeantet Prize Charitable Trust (Charity Number 1011770). G.A. discloses support for the research of this work from the University of Cambridge start-up funds. A.R.T. discloses support for the research of this work from the Chinese Academy of Medical Sciences (CAMS) Chinese Innovation Fund for Medical Science (CIFMS), China (grant no. 2018-I2M-2-002). P.J.B. discloses support for the research of this work from the National Institutes of Health (NIH grant no. AI165075), Caltech Merkin Institute and George Mason University Fast Grant.

Sequences of constructs are available in GenBank, as described in the section ‘Plasmids and cloning’. Plasmids encoding pDEST14-SpySwitch, pET28a-SpyCatcher003-mi3, pET28a-SpyTag-MBP, pcDNA3.1-SpyTag-SARS2 RBD Wuhan, pcDNA3.1-SpyTag-SARS2 RBD Delta, pcDNA3.1-SpyTag-SARS2 RBD BQ.1.1, pcDNA3.1-SpyTag-SARS2 RBD XBB.1.5, pcDNA3.1-SpyTag-Quartet, pcDNA3.1-Alternate Quartet, pcDNA3.1-Kraken Quartet, pcDNA3.1-Quartet [SARS1] and pcDNA3.1-SpyTag-Quartet_No_Linker have been deposited in the Addgene repository (https://www.addgene.org/Mark_Howarth/). Source data are provided with this paper. Requests for further information and/or resources and reagents should be directed to and will be fulfilled by the lead contact, M.R.H. (mh2186@cam.ac.uk).

M.R.H. is an inventor on a patent on spontaneous amide bond formation (EP2534484) and a SpyBiotech co-founder and shareholder. M.R.H. and A.H.K. are inventors on a patent on SpyTag003:SpyCatcher003 (UK Intellectual Property Office 1706430.4). P.J.B. and A.A.C. are inventors on a US patent application filed by the California Institute of Technology that covers the methodology to generate cross-reactive antibodies using Mosaic nanoparticles. P.J.B. and A.A.C. are inventors on a US patent application filed by the California Institute of Technology that covers the monoclonal antibodies elicited by vaccination with Mosaic nanoparticles described in this work. P.J.B., A.A.C. and J.R.K. are inventors on a US patent application filed by the California Institute of Technology that covers the methods of isolating cross-reactive antibodies by vaccination with Mosaic nanoparticles. All other authors have no competing interests to declare.