The SARS-CoV-2 spike protein remains the central target for vaccines, therapeutic antibodies, and serological assays, but ongoing viral evolution has introduced significant mutations—especially within the RBD—that can alter antibody binding and reduce neutralization potency. As circulating variants continue to diverge from the original 2020 spike, reliance on early-generation reagents is no longer sufficient. For research, diagnostics, and vaccine development, updated spike constructs and antibodies that maintain activity across variant lineages—or are specifically tailored to current sequences—are increasingly essential.