Potential determinants of antibody responses after vaccination against SARS-CoV-2 in older persons: the Doetinchem Cohort Study

Yunus Kuijpers; H Susan J Picavet; Lia de Rond; Mary-Lène de Zeeuw-Brouwer; Ryanne Rutkens; Esther Gijsbers; Irene Slits; Peter Engelfriet; Anne-Marie Buisman; W M Monique Verschuren

doi:10.1186/s12979-023-00382-4

Potential determinants of antibody responses after vaccination against SARS-CoV-2 in older persons: the Doetinchem Cohort Study

Immun Ageing. 2023 Oct 25;20(1):57. doi: 10.1186/s12979-023-00382-4.

Affiliations

¹ Centre for Prevention, Lifestyle and Health, National Institute for Public Health and the Environment (RIVM), Bilthoven, 3721 MA, The Netherlands. Yunus.Kuijpers@rivm.nl.
² Centre for Prevention, Lifestyle and Health, National Institute for Public Health and the Environment (RIVM), Bilthoven, 3721 MA, The Netherlands.
³ Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment (RIVM), Bilthoven, 3721 MA, The Netherlands.
⁴ Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, 3508 TC, The Netherlands.

Abstract

Background: Immune responses to vaccination vary widely between individuals. The aim of this study was to identify health-related variables potentially underlying the antibody responses to SARS-CoV-2 vaccination in older persons. We recruited participants in the long-running Doetinchem Cohort Study (DCS) who underwent vaccination as part of the national COVID-19 program, and measured antibody concentrations to SARS-CoV-2 Spike protein (S1) and Nucleoprotein (N) at baseline (T0), and a month after both the first vaccination (T1), and the second vaccination (T2). Associations between the antibody concentrations and demographic variables, including age, sex, socio-economic status (SES), comorbidities (cardiovascular diseases and immune mediated diseases), various health parameters (cardiometabolic markers, inflammation markers, kidney- and lung function) and a composite measure of frailty ('frailty index', ranging from 0 to 1) were tested using multivariate models.

Results: We included 1457 persons aged 50 to 92 years old. Of these persons 1257 were infection naïve after their primary vaccination series. The majority (N = 954) of these individuals were vaccinated with two doses of BNT162b2 (Pfizer) and their data were used for further analysis. A higher frailty index was associated with lower anti-S1 antibody responses at T1 and T2 for both men (R_T1 = -0.095, P_T1 = 0.05; R_T2 = -0.11, P_T2 = 0.02) and women (R_T1 = -0.24, P_T1 < 0.01; R_T2 = -0.15, P_T2 < 0.01). After correcting for age and sex the frailty index was also associated with the relative increase in anti-S1 IgG concentrations between the two vaccinations (β = 1.6, P < 0.01). Within the construct of frailty, history of a cardiac catheterization, diabetes, gastrointestinal disease, a cognitive speed in the lowest decile of the population distribution, and impaired lung function were associated with lower antibody responses after both vaccinations.

Conclusions: Components of frailty play a key role in the primary vaccination response to the BNT162b2 vaccine within an ageing population. Older persons with various comorbidities have a lowered immune response after their first vaccination, and while frail and sick older persons see a stronger increase after their second vaccination compared to healthy people, they still have a lower antibody response after their second vaccination.

Keywords: Age; Antibody responses; COVID-19 vaccination; Comorbidity; Frailty; Lifestyle deficits.