mRNA vaccination in octogenarian nuns 15 and 20 months after recovery from COVID-19 elicits robust immune and antibody responses that include Omicron

Knowledge about the impact of prior SARS-CoV-2 infection of the elderly on mRNA vaccination response is needed to appropriately address the demand for additional vaccinations in this vulnerable population. Here we show that octogenarians, a high-risk population, mount a sustained SARS-CoV-2 spike-specific IgG antibody response for 15 months following infection. This response boosts antibody levels 35-fold upon receiving a single dose of BNT162b2 mRNA vaccine 15 months after recovery from COVID-19. In contrast, antibody responses in naïve individuals boost only 6-fold after a second vaccine. Spike-specific ACE2 antibody binding responses in the previously infected octogenarians following two vaccine doses exceed those found in a naïve cohort after two doses. RNA-seq demonstrates activation of interferon-induced genetic programs, which persist only in the previously infected. A preferential increase of specific IGHV clonal transcripts that are the basis of neutralizing antibodies is observed only in the previously infected nuns. Overall design: RNA-seq were performed with peripheral blood mononuclear cells (PBMCs) from recovered COVID-19 patients and naïve individuals who had received the BNT162b mRNA vaccine.