Enhancing the Deformability of the Adjuvant: Achieving Lymph Node Targeted Delivery to Elicit a Long‐Lasting Immune Protection

A key challenge in vaccine development is to induce an effective and durable immune response. Live virus vaccines induce lifelong antibody responses; however, the immune responses induced by inactivated or subunit vaccines decrease gradually. Activation of the germinal center (GC) reaction, which generates long-lived plasma cells (LLPCs), is a key mediator of long-term antibody responses. To enhance the activation of GC, lymph node-targeted delivery of the vaccine is promoted by enhancing the deformability of the delivery vector. In this study, a double emulsion is designed with strong deformability and containing chitosan nanoparticles (CSNP) in the internal aqueous phase (W_NP) for efficient antigen loading, called W_NP/O/W. The flexible oil layer and the internally loaded positively charged particles endow the emulsion with strong deformability, continuously enrich model antigen ovalbumin (OVA) in the lymph nodes, activate germinal center B (GC B) cells and T follicular helper (T_FH) cells, induce LLPCs, and obtain high-level antibody persistence for more than 5 months, which is significantly better than the traditional oil emulsion adjuvant. Concurrently, it also improves the immune-protective effect in aged mice. Altogether, these results indicate that W_NP/O/W achieves lymph node targeted delivery by strengthening deformability, generating high-intensity antibody responses, and long-lasting immune protection.