Reduced antibody acquisition with increasing age following vaccination with BNT162b2: results from a large study performed in the general population aged 12 to 92 years

Vaccine-induced protection of the population against severe COVID-19, hospitalization and death is of 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 vaccination. 1·735 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 doses of vaccine. S1 IgG was higher in participants with a history of SARS-CoV-2 infection (median: 4·535 BAU/ml, IQR: 2·341-7·205) compared to infection-naïve persons (1·842 BAU/ml, 1·019-3·116) after two doses, p<0.001. In infection-naïve persons, linear mixed effects regression showed a strong negative association between age and S1 IgG one month after the first vaccination (p<0.001) across the entire age range. The association was still present after the second vaccination, but less pronounced. Females had higher S1 IgG than males after both the first and second vaccination (p<0.001); although this difference was lower after the second dose. In persons with an infection history, age nor sex was associated with peak S1 IgG. As IgG decreased with age and time since vaccination, older persons may become at risk of infection, especially with escape variants such as Omicron. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by the Dutch Ministry of Health, Welfare and Sports ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained through The Medical Research Ethics Committee Utrecht for both the 50+ population cohort (NL74843.041.21, EudraCT: 2021-001976-40), and for the adolescent and adult cohort (12-60 years) (NL76440.041.21, EudraCT: 2021-001357-31). All participants provided written informed consent. In the case of participants aged 12 till 16, both parents also provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors