A Synthetic Liposome Nanoparticle Vaccine Platform for Broad-Spectrum Vaccine Design

Emerging viruses such as SARS-CoV-2 and HIV-1 pose major challenges for traditional vaccines due to their rapid mutation and immune evasion. Here, we present a modular liposomal nanoparticle (LNP) vaccine platform integrating trimeric immunogens and synergistic adjuvants to induce broad and durable immunity. Using a self-assembled SARS-CoV-2 RBD trimer (RM) based on MTQ and Ni2+/His-tag coupling, antigens were directionally displayed on LNPs coloaded with QS-21, MPLA, and R848 adjuvants. This RM-LNP formulation enhanced antigen stability, lymph node targeting, and germinal center responses, eliciting high titers of broadly neutralizing antibodies and strong T and memory B cell immunity. The RM-LNP vaccine conferred potent neutralization against Omicron subvariants and protected hACE2 mice from Delta, BA.5, and XBB infection. Extension to HIV-1 vaccine design also demonstrated significant and broad neutralization against Tier 2 strains. This study offers a versatile nanovaccine strategy for combating highly mutable viruses.