Needle-free pan-sarbecovirus vaccine clears phase 1 safety milestone, but broad protection remains unproven

Summary This open-label, first-in-human phase 1 dose-escalation trial evaluated the DNA vaccine pEVAC-PS, a computationally designed pan-sarbecovirus candidate delivered intradermally by needle-free PharmaJet Tropis in healthy adults aged 18–50 years with prior COVID-19 vaccination. Thirty-nine participants received two doses on days 0 and 28 across four dose levels (0.2, 0.4, 0.8, 1.2 mg); the primary endpoints were safety/reactogenicity and secondary endpoints were humoral immunogenicity at day 56. No serious adverse reactions or serious adverse events occurred, and reactogenicity was generally mild, with grade 3 events attributed to intercurrent COVID-19 rather than vaccination. Immunogenicity was modest: binding responses showed limited increases, neutralization rose only modestly against Omicron BA.1 or Delta in higher-dose groups, and cross-neutralization to SARS-CoV-1 remained unchanged despite conserved-epitope recognition. Comment: This is a useful and encouraging first-in-human study demonstrating that a needle-free, intradermal DNA pan-sarbecovirus vaccine can be administered safely and feasibly in adults. Although the immunogenicity signals were modest and...