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The M2-deficient Single Replication (M2SR) influenza virus is a novel vaccine platform designed to provide broad protection against various influenza strains (FluGen, 2024). Unlike traditional live attenuated influenza vaccines, M2SR lacks the M2 ion channel gene, which is essential for the release of the viral genome into the host cell cytoplasm and the assembly of new infectious particles (Eichelberger et al., 2018). Consequently, the virus can enter a host cell and undergo a single round of replication, expressing the entire internal and surface protein complement of the virus, but it cannot spread to neighboring cells (Sarawar et al., 2016). This mechanism triggers a comprehensive immune response that includes mucosal, humoral, and cellular components, potentially offering superior efficacy compared to standard-of-care vaccines (NCT03999138). M2SR is primarily being developed as a supra-seasonal or universal influenza vaccine candidate to address the challenges of viral drift and mismatch (FluGen, 2024). Clinical studies have demonstrated that the M2SR platform is well-tolerated and capable of inducing cross-reactive immunity against drifted strains (NCT04096131).
The M2SR virus lacks the M2 ion channel, allowing it to infect host cells and express a full complement of viral proteins without producing infectious progeny; this single-replication cycle induces mucosal, humoral, and cellular immunity (FluGen, 2024; Eichelberger et al., 2018).
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