This study characterizes the biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens incorporating mutations from the B.1.351 (β) and P.1 (γ) variants of concern (VOCs). It also demonstrates the adaptability of the RBD-NP platform to Omicron strains BA.5 and XBB.1.5, comparing variant immunogens to the ancestral Wu-1 RBD and prefusion-stabilized (HexaPro) spike trimers. The research finds that immunogen properties can differ substantially, impacting variant vaccine development. Stabilizing mutations increased physical stability without affecting immunogenicity. Both RBD-NP immunogens and HexaPro trimers elicited comparable neutralizing antibody levels against VOCs. The study concludes that RBD-NP-based vaccines can elicit neutralizing antibody responses against SARS-CoV-2 variants and can be rapidly designed and stabilized, showcasing their potential as a broadly protective coronavirus vaccine platform.

Marcos C. Miranda, Elizabeth Kepl, Mary Jane Navarro, Chengbo Chen, Max Johnson, Kaitlin R. Sprouse, Cameron Stewart, Anne Palser, Adian Valdez, Deleah Pettie, Claire Sydeman, Cassandra Ogohara, John C. Kraft, Minh Pham, Michael Murphy, Sam Wrenn, Brooke Fiala, Rashmi Ravichandran, Daniel Ellis, Lauren Carter, Davide Corti, Paul Kellam, Kelly Lee, Alexandra C. Walls, David Veesler, Neil P. King