{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:05:48Z","timestamp":1791331548640,"version":"4.3.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Needle-free injection system (NFIS) is easy to operate and can decrease needle phobia. Besides, NFIS can increase the interaction of antigens in a more dispersed manner with immune cell at local injection site, which may improve the immune responses of mRNA vaccines. Although SARS-CoV-2 mRNA vaccines have great success, universal vaccines are urgently needed. Delivering universal mRNA vaccines by NFIS is preferred to combat COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RBD3-Fc mRNA expressing BA.4, Delta, and prototype RBD, and human IgG Fc with YTE mutation was designed and synthesized. The safety and immune responses of universal RBD3-Fc naked mRNA and mRNA-LNP vaccines delivered intradermally using NFIS (named GV-01) and intramuscularly via needles were evaluated and compared in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The prime-boost regimen administered by two routes resulted in potent immune responses and intradermal delivery displays comparable or better performance in terms of binding antibodies, neutralizing antibodies and T cell responses. Naked mRNA vaccines were functional, but less effective than mRNA-LNP vaccines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The above results suggest that RBD3-Fc vaccines are safe and immunogenic and NFIS can be used as an alternative to needles\/syringes for the inoculation of mRNA-LNP vaccines to elicit robust systematic immune responses.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1530736","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T05:12:15Z","timestamp":1739769135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Intradermal delivery of SARS-CoV-2 RBD3-Fc mRNA vaccines via a needle-free injection system induces robust immune responses in 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