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

Knowledge about the impact of prior severe acute respiratory syndrome coronavirus 2 (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 immunoglobulin G (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 coronavirus disease 2019 (COVID-19). In contrast, antibody responses in naive individuals boost only 6-fold after a second vaccine. Spike-specific angiotensin-converting enzyme 2 (ACE2) antibody binding responses in the previously infected octogenarians following two vaccine doses exceed those found in a naive cohort after two doses. RNA sequencing (RNA-seq) demonstrates activation of interferon-induced genetic programs, which persist only in the previously infected. A preferential increase of specific immunoglobulin G heavy chain variable (IGHV) clonal transcripts that are the basis of neutralizing antibodies is observed only in the previously infected nuns.

Robust immune response to the BNT162b mRNA vaccine in an elderly population vaccinated 15 months after recovery from COVID-19.

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.

Robust immune response to the BNT162b mRNA vaccine in an elderly population vaccinated 15 months after recovery from COVID-19

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-naive 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 naive 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.