Nursing home (NH) residents have experienced significant morbidity and mortality to SARS-CoV-2 throughout the pandemic. Vaccines initially curbed NH resident morbidity and mortality, but antibody levels and protection have declined with time since vaccination, prompting introduction of booster vaccination. This study assesses humoral immune response to booster vaccination in 85 NH residents and 44 health care workers (HCW) that we have followed longitudinally since initial SARS-CoV-2 BNT162b2 mRNA vaccination. The findings reveal that booster vaccination significantly increased anti-spike, anti-receptor binding domain, and neutralization titers above the pre-booster levels in almost all NH residents and HCW to significantly higher levels than shortly after the completion of the initial vaccine series. These data support the CDC recommendation to offer vaccine boosters to HCWs and NH residents on an immunological basis. Notably, even the older, more frail and more multi-morbid NH residents have sizable antibody increases with boosting.