Programmable Stapling Peptide Based on Sulfonium as Universal Vaccine Adjuvants for Multiple Types of Vaccines

Abstract Adjuvants are non‐specific immune enhancers commonly used to improve the responsiveness and persistence of the immune system toward antigens. However, due to the undefined chemical structure, toxicity, non‐biodegradability, and lack of design technology in many existing adjuvants, it remains difficult to achieve substantive breakthroughs in the adjuvant research field. Here, a novel adjuvant development strategy based on stapling peptides is reported to overcome this challenge. The nano‐vaccine incorporating peptide adjuvant and recombinant HBsAg protein not only induced strong antibody titers that are equivalent to aluminum adjuvanted vaccines but also simultaneously activated T‐cell immune response. Similar results are also observed in herpes zoster vaccine and more complex influenza vaccine. The mechanism analysis demonstrates that antigen is efficiently carried into antigen‐presenting cells (APCs) by peptide, further promoting the secretion of cytokines and activation of APCs. In addition, by redesigning the adjuvant, it is found that the sulfonium centers, rather than the sequence of peptide played an important role in immune activation. This discovery may provide a new paradigm for the rational design of peptide‐based adjuvants. In brief, this study demonstrates that stapling peptides with sulfonium centers can provide a well‐defined, programmable, biocompatible, and effective adjuvant for multiple types of vaccines.