Reduced Antibody Acquisition with Increasing Age following Vaccination with BNT162b2: Results from Two Longitudinal Cohort Studies in The Netherlands

Abstract

Vaccine-induced protection against severe COVID-19, hospitalization, and death is of the utmost importance, especially in the elderly. However, limited data are available on humoral immune responses following COVID-19 vaccination in the general population across a broad age range. We performed an integrated analysis of the effect of age, sex, and prior SARS-CoV-2 infection on Spike S1-specific (S1) IgG concentrations up to three months post-BNT162b2 (Pfizer/BioNTech; Comirnaty) vaccination. In total, 1735 persons, eligible for COVID-19 vaccination through the national program, were recruited from the general population (12 to 92 years old). Sixty percent were female, and the median vaccination interval was 35 days (interquartile range, IQR: 35–35). All participants had seroconverted to S1 one month after two vaccine doses. S1 IgG was higher in participants with a history of SARS-CoV-2 infection (median: 4535 BAU/mL, IQR: 2341–7205) compared to infection-naive persons (1842 BAU/mL, 1019–3116), p < 0.001. In infection-naive persons, linear mixed effects regression showed a strong negative association between age and S1 IgG (p < 0.001) across the entire age range. Females had higher S1 IgG than males (p < 0.001). In persons with an infection history, age nor sex was associated with S1 IgG concentrations. The lower magnitude of S1 antibodies in older persons following COVID-19 vaccination will affect long-term protection.

COVID-19 vaccination-induced antibody responses and waning by age and comorbidity status in a large population-based prospective cohort study

“…In line with our results, lower S-antibody levels shortly after vaccination among those of higher age or with medical conditions have been reported for the primary series (2-5, 15, 16). Also, Sanada et al .…”

“…Vaccine product could also potentially affect the peak levels that are reached. Although almost all participants seroconverted within 3 months following the primary series (regardless of vaccine product), we observed large differences between vaccines in GMC at 2-6 weeks following the primary series, with the highest response observed for Spikevax and the lowest for Vaxzevria, as has been reported in other studies (2-4, 6, 7, 23). A role for the different mechanisms of mRNA versus vector based vaccines has been hypothesized.…”

“…Booster doses have been reported to produce higher antibody concentrations than after the previous dose (5, 11). Age-dependent antibody responses have been reported after the primary series, with younger persons reaching higher levels (2, 5, 11). In the study by Wei et al, this effect was also observed after the first booster (5).…”

“…In the study by Wei et al, this effect was also observed after the first booster (5). However, differences between age groups have been reported to become smaller with increasing number of doses (2, 11). In the Netherlands, people with asplenia, diabetes, cardiovascular disease, immune disorder, cancer with current or no treatment, lung disease or asthma, hepatic disease, neurological disease, renal disease, organ or bonemarrow transplantation were prioritized for the primary series and booster vaccinations.…”

“…It has been shown that COVID-19 vaccines produce robust S-antibody responses after the primary series, and these responses are increased further following booster vaccinations. S-antibody concentrations have been reported to be higher for mRNA vaccines compared to viral vector vaccines and varying results were reported on the magnitude and/or duration of S-antibody responses by age and underlying medical conditions (2-7). Assessing the antibody response in vulnerable groups is valuable since SARS-CoV-2 S-antibody concentrations may be an indicator for protection against infection (5, 8, 9).…”