Programmable Antigen‐Specific Immunity via Self‐Adjuvanting Nanovaccines Co‐Delivering Immune Modulators

Abstract Cancer peptide vaccines harness the host immune system to generate tumor‐specific immune responses, offering potential for treating metastatic cancers and preventing recurrence. However, the limited immunogenicity of peptide antigens restricts their clinical efficacy, necessitating strategies to enhance their potency. One promising approach involves the conjugation of antigens with adjuvants to elicit antigen‐specific immune responses, thereby creating self‐adjuvanting vaccines. In this study, we developed an improved platform for such vaccines. Specifically, the antigenic CH401 peptide was conjugated with the adjuvant (Pam 3 CSK 4 ) and formulated into cationic lipid nanoparticles (LNPs) smaller than 100 nm to facilitate uptake by immune cells, with supplemental adjuvants incorporated to modulate immune responses. Notably, the microflow device iLiNP enabled precise, size‐controlled LNP formulation from various components, supporting the systematic evolution of the self‐adjuvanting vaccine platform. These vaccine candidates demonstrated enhanced immunogenicity, enabling precise modulation of immune responses in an antigen‐specific manner. Notably, these vaccines elicited potent immune responses in humanized mouse models. Overall, this strategy represents a next‐generation self‐adjuvanting vaccine platform, capable of both enhancing and fine‐tuning antigen‐specific immune responses, holding great promise for innovative vaccine development.