ArticleCell reports2026
mRNA delivery of mosaic-8 pan-sarbecovirus RBD vaccines elicits distinct antibody epitope signatures.
Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Protein-based mosaic-8 nanoparticles displaying eight SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) elicited broadly cross-reactive antibodies that could protect from zoonotic spillovers. Here, we extend the mosaic-8 concept to mRNA by encoding membrane-bound RBD quartets (four linked RBDs) as dual quartet RBD-mRNA and dual quartet RBD-EABR-mRNA, the latter leveraging ESCRT- and ALIX-binding region (EABR) technology for display on cell surfaces and secreted virus-like particles. Compared with protein-based mosaic-8, mRNA-encoded mosaic-8 induced equivalent or enhanced antibody breadth, neutralization potencies, and conserved epitope targeting, while eliciting enhanced T cell responses and more balanced IgG subclass profiles consistent with potentially superior Fc effector functions. Finally, systems serology-polyclonal epitope mapping (SySPEM) revealed distinct IgG-subclass-specific epitope signatures across mRNA, EABR-mRNA, and protein vaccines, demonstrating that the mode of antigen display can shape epitope recognition. Successful conversion of a multivalent protein vaccine to mRNA platforms informs the design of broadly protective vaccines and advances mosaic-8 toward clinical development.
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