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In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only\u2013immunized animals. Importantly, pADA significantly improved the longevity of these enhanced responses in vivo. This coincided with durable increases in frequencies of plasmablasts, receptor-binding domain\u2013specific memory B cells, and SARS-CoV-2\u2013specific T follicular helper cells. Increased spike-specific T cell polyfunctionality was also observed. Notably, animals coimmunized with pADA had significantly reduced viral loads compared with their nonadjuvanted counterparts in a SARS-CoV-2 infection model. These data suggest that pADA enhances immune memory and durability and supports further translational studies.<\/jats:p>","DOI":"10.4049\/jimmunol.2200056","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T18:19:23Z","timestamp":1657649963000},"page":"118-127","source":"Crossref","is-referenced-by-count":7,"title":["Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1"],"prefix":"10.1093","volume":"209","author":[{"given":"Gina M","family":"Cusimano","sequence":"first","affiliation":[{"name":"Department of Medicine, Drexel University College of Medicine , Philadelphia, PA"},{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebony N","family":"Gary","sequence":"additional","affiliation":[{"name":"The Vaccine & Immunotherapy Center, The Wistar Institute , 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