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Herein, a general pro\u2010antigen strategy for subunit vaccine development based on the reversibly formulated receptor binding domain of SARS\u2010CoV\u20102 spike protein (S\u2010RBD) is reported. Since the poor lymph node targeting and uptake of S\u2010RBD by antigen\u2010presenting cells prevent effective immune responses, S\u2010RBD protein is formulated into a reversible nanogel (S\u2010RBD\u2010NG), which serves as a pro\u2010antigen with enhanced lymph node targeting and dendritic cell and macrophage accumulation. Synchronized release of S\u2010RBD monomers from the internalized S\u2010RBD\u2010NG pro\u2010antigen triggers more potent immune responses in vivo. In addition, by optimizing the adjuvant used, the potency of S\u2010RBD\u2010NG is further improved, which may provide a generally applicable, safer, and more effective strategy for subunit vaccine development against SARS\u2010CoV\u20102 as well as other viruses.<\/jats:p>","DOI":"10.1002\/smll.202004237","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T06:06:33Z","timestamp":1603778793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Severe Acute Respiratory Syndrome Coronavirus\u20102 Spike Protein Nanogel as a Pro\u2010Antigen Strategy with Enhanced Protective Immune Responses"],"prefix":"10.1002","volume":"16","author":[{"given":"Long","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education College of Chemistry and Molecular 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