Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice.

Autor:	Cohen AA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Gnanapragasam PNP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Lee YE; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Hoffman PR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Ou S; 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., Keeffe JR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Wu HJ; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Howarth M; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., West AP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Barnes CO; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA., Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2021 Jan 05. Date of Electronic Publication: 2021 Jan 05.
DOI:	10.1101/2020.11.17.387092
Abstrakt:	Protection against SARS-CoV-2 and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor-binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles; 4-8 distinct RBDs). Mice immunized with RBD-nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic-RBD-nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs compared to sera from immunizations with homotypic SARS-CoV-2-RBD-nanoparticles or COVID-19 convalescent human plasmas. Moreover, sera from mosaic-RBD-immunized mice neutralized heterologous pseudotyped coronaviruses equivalently or better after priming than sera from homotypic SARS-CoV-2-RBD-nanoparticle immunizations, demonstrating no immunogenicity loss against particular RBDs resulting from co-display. A single immunization with mosaic-RBD-nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses. Competing Interests: 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.
Databáze:	MEDLINE
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