Kang et. al describe the fabrication of three SARS-CoV-2 S RBD-conjugated nanoparticle vaccine candidates which target the RBD of a SARS-CoV-2 S glycoprotein. Conjugation to nanoparticles enables multivalent antigen presentation and the ability of the vaccine candidate to evoke an immune response, as well as rapid manufacturability. The three candidates developed are enabled by SpyTag-SpyCatcher bioconjugation technology and include RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer). To first confirm the production quality and structural stability of each candidate, SEC, SDS-PAGE analysis, and electron microscopy were performed. Nano differential scanning fluorimetry (nanoDSF) was performed on the RBD monomer and the RBD-conjugated NPs to evaluate thermostability. The antigenicity of RBD-conjugated NPs was characterized in vitro through binding affinity and kinetic studies between the RBD-conjugated NPs and RBD-specific antibodies. After performing an ELISA, the resulting profile showed that the RBD-conjugated NPs bound to the antibodies in a dose-dependent manner. In addition, in vivo, adjuvanted RBD-conjugated NPs elicited 71.8 to 168.4-fold higher antibody serum titers than those of the adjuvanted RBD monomer. Neutralizing assays of SARS-CoV-2 virus in immunized mice sera showed that the RBD-NPs outperformed the RBD monomer. The group highlights the universality of their nanoparticle-conjugation platform favored for future vaccine development, competitive efficiency, and rapid manufacturing.