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Because of its small size, most preclinical and early clinical efforts have focused on multimerizing RBD on various formats of nanoparticles to increase its immunogenicity. Using an easily administered injectable hydrogel scaffold that is rationally designed for enhanced retainment of RBD, an alternative and facile approach for boosting RBD immunogenicity in mice is demonstrated. Prolonged delivery of poly (I:C) adjuvanted RBD by the hydrogel scaffold results in sustained exposure to lymphoid tissues, which elicits serum IgG titers comparable to those induced by three bolus injections, but more long\u2010lasting and polarized toward T<jats:sub>H<\/jats:sub>1\u2010mediated IgG2b. The hydrogel scaffold induces potent germinal center (GC) reactions, correlating with RBD\u2010specific antibody generation and robust type 1 T cell responses. Besides being an enduring RBD reservoir, the hydrogel scaffold becomes a local inflammatory niche for innate immune cell activation. Collectively, the injectable hydrogel scaffold provides a simple, practical, and inexpensive means to enhance the efficacy of RBD\u2010based subunit vaccines against COVID\u201019 and may be applicable to other circulating and emerging pathogens.<\/jats:p>","DOI":"10.1002\/adhm.202101714","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T03:13:07Z","timestamp":1636513987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Sustained Delivery of SARS\u2010CoV\u20102 RBD Subunit Vaccine Using a High Affinity Injectable Hydrogel Scaffold"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-0349","authenticated-orcid":false,"given":"Jing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Engineering Cornell University  Ithaca NY 14853 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