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To counter this constant evolution, seasonal vaccines are redesigned annually on predictions of what will be the dominant circulating variants in the upcoming flu season. Predictions must be made significantly ahead of time owing to the time needed to manufacture sufficient doses of vaccine, which can lead to mismatches between vaccine and circulating strains that almost universally lead to limited efficacy

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The Multiple Fold (mfold) web server is a widely used bioinformatics tool for identifying secondary structures of ssDNA (73), using thermodynamic approaches like Turners thermodynamics table and free-energy minimization algorithms to forecast hybridization and melting temperatures (74)