Knowledge about the impact of prior SARS-CoV-2 infection of the elderly on mRNA vaccination response is needed to appropriately address the need for booster vaccination in this vulnerable population. To address this, we investigated antibody and genomic immune responses in 16 elderly (avg. 81 yrs.) individuals that had received a single booster dose of BNT162b vaccine 15 months after recovering from COVID-19. Spike-specific IgG antibody levels increased in each of the study participants from an average of 710 U/ml prior to the vaccination to more than 40,000 U/ml within ten weeks after the vaccination. In contrast, anti-spike-specific IgG antibody levels averaged 2,190 U/ml in 14 healthy SARS-CoV-2-naïve individuals (avg. 58 yrs.) ten weeks after the second dose of BNT162b. RNA-seq conducted on PBMCs demonstrated the activation of interferon-activated genetic programs in both cohorts within one day. Unlike their transient induction in the younger naïve population, persistent activity and the initiation of additional cell cycle regulated programs were obtained in the older COVID-19 recovered population. Here we show that the elderly, a high-risk population, can mount a strong antibody and a persistent molecular immune response upon receiving a single dose of mRNA vaccine 15 months after recovery from COVID-19.