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The RNActive seasonal influenza vaccine is a first-generation mRNA-based vaccine candidate developed by CureVac. Unlike later mRNA vaccines that utilize lipid nanoparticles (LNPs), the RNActive platform employs a proprietary formulation where the mRNA is complexed with the cationic protein protamine. This vaccine is designed to encode the full-length hemagglutinin (HA) surface glycoprotein of various influenza virus strains, including seasonal A (H1N1, H3N2) and B strains, as well as avian strains like H5N1. The protamine component serves a dual purpose: it stabilizes the mRNA and acts as an adjuvant by stimulating Toll-like receptors 7 and 8 (TLR7/8). Clinical evaluation in Phase 1 trials demonstrated that the vaccine could be administered intradermally or intramuscularly and was capable of inducing functional antibodies, although the immunogenicity of this protamine-complexed format was generally lower than that observed with subsequent LNP-formulated mRNA technologies.
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