SARS-CoV‑2 B Epitope-Guided Neoantigen NanoVaccines Enhance Tumor-Specific CD4/CD8 T Cell Immunity through B Cell Antigen Presentation

Current neoantigen cancer vaccines activate T cell immunity through dendritic cell/macrophage-mediated antigen presentation. It is unclear whether incorporating B cell-mediated antigen presentation into current neoantigen vaccines could enhance CD4/CD8 T cell immunity to improve their anticancer efficacy. We developed SARS-CoV-2 B cell epitope-guided neoantigen peptide/mRNA cancer nanovaccines (B_SARST_NeoAgVax) to improve anticancer efficacy by enhancing tumor-specific CD4/CD8 T cell antitumor immunity through B cell-mediated antigen presentation. B_SARST_NeoAgVax cross-linked with B cell receptor, promoted SARS-CoV-2 B cell-mediated antigen presentation to tumor-specific CD4 T cells, increased tumor-specific follicular/nonfollicular CD4 T cells, and enhanced B cell-dependent tumor-specific CD8 T cell immunity. B_SARST_NeoAgVax achieved superior efficacy in melanoma, pancreatic, and breast cancer models compared with the current neoantigen vaccines. Our study provides a universal platform, SARS-CoV-2 B epitope-guided neoantigen nanovaccines, to improve anticancer efficacy against various cancer types by enhancing CD4/CD8 T cell antitumor immunity through viral-specific B cell-mediated antigen presentation.