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.

Automated summary

The study reveals that octogenarians who were previously infected with SARS-CoV-2 demonstrate a sustained IgG antibody response for 15 months and exhibit a 35-fold increase in antibody levels after receiving a single dose of the BNT162b2 mRNA vaccine. In contrast, antibody responses in naive individuals only increase by 6-fold after the second vaccine dose. Furthermore, the previously infected elderly individuals show higher spike-specific ACE2 antibody binding responses after two vaccine doses compared to the naive cohort. RNA sequencing analysis indicates the activation of interferon-induced genetic programs in the previously infected individuals, and a preferential increase of specific IGHV clonal transcripts is observed only in the previously infected nuns.