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

Abstract 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.