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COVID-19 mRNA Vaccine Immunogenicity in Immunosuppressed Individuals. Individuals on immunosuppressive (IS) therapy have increased mortality from SARS-CoV-2 infection, and delayed viral clearance may lead to new viral variants.1 IS therapy reduces antibody responses following COVID-19 messenger RNA (mRNA) vaccination;2-5 however, a comprehensive assessment of vaccine immunogenicity is lacking. Here we show that IS therapy reduced neutralizing, binding, and non-neutralizing antibody functions in addition to CD4 and CD8 T cell IFN-γresponses following COVID-19 mRNA vaccination compared to immunocompetent individuals. Moreover, IS therapy reduced cross-reactivity against SARS-CoV-2 variants. These data suggest that the current COVID-19 mRNA vaccine regimens will likely not provide optimal protection in immunocompromised individuals.