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However, due to the undefined chemical structure, toxicity, non\u2010biodegradability, 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\u2010vaccine 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\u2010cell 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\u2010presenting 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\u2010based adjuvants. In brief, this study demonstrates that stapling peptides with sulfonium centers can provide a well\u2010defined, programmable, biocompatible, and effective adjuvant for multiple types of vaccines.<\/jats:p>","DOI":"10.1002\/advs.202409567","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T07:51:12Z","timestamp":1738137072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Programmable Stapling Peptide Based on Sulfonium as Universal Vaccine Adjuvants for Multiple Types of Vaccines"],"prefix":"10.1002","volume":"12","author":[{"given":"Yaping","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemical Oncogenomics School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School  Shenzhen 518055 P. R. China"},{"name":"Pingshan Translational Medicine Center Shenzhen Bay Laboratory  Shenzhen 518118 P. R. 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