The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 
(SARS-CoV-2) and its variants has resulted in global economic losses and posed a threat to human health. The 
pandemic highlights the urgent need for an efficient, easily producible, and broad-spectrum vaccine. Here, we 
present a potentially universal strategy for the rapid and general design of vaccines, focusing on the design and 
testing of omicron BA.5 RBD-conjugated self-assembling ferritin nanoparticles (NPs). The covalent bonding of 
RBD-Fc to protein A-ferritin was easily accomplished through incubation, resulting in fully multivalent RBDconjugated NPs that exhibited high structural uniformity, stability, and efficient assembly. The ferritin nanoparticle vaccine synergistically stimulated the innate immune response, Tfh-GCB-plasma cell-mediated activation 
of humoral immunity and IFN-γ-driven cellular immunity. This nanoparticle vaccine induced a high level of 
cross-neutralizing responses and protected golden hamsters challenged with multiple mutant strains from 
infection-induced clinical disease, providing a promising strategy for broad-spectrum vaccine development for 
SARS-CoV-2 prophylaxis. In conclusion, the nanoparticle conjugation platform holds promise for its potential 
universality and competitive immunization efficacy and is expected to facilitate the rapid manufacturing and 
broad application of next-generation vaccines.