Abstract
Background: Older persons elicit heterogeneous antibody responses to vaccinations that generally are lower than those in younger, healthier individuals. As older age and certain comorbidities can influence these responses we aimed to identify health-related variables associated with antibody responses after repeated SARS-CoV-2 vaccinations and its persistence thereafter in SARS-CoV-2 infection-naïve and previously infected older persons.
Method: In a large longitudinal study of older persons of the general population 50 years and over, a sub-cohort of the longitudinal Doetinchem cohort study (n=1374), we measured antibody concentrations in serum to SARS-CoV-2 Spike protein (S1) and Nucleoprotein (N). Samples were taken following primary vaccination with BNT162b2 or AZD1222, and pre- and post-vaccination with a third, fourth BNT162b2 or mRNA-1273 (Wuhan), and a fifth BNT162b2 bivalent (Wuhan/Omicron BA.1) vaccine. Associations between persistence of antibody concentrations over time and age, sex, health characteristics including cardiovascular and inflammatory diseases as well as a frailty index were tested using univariate and multivariate models .
Results: The booster doses substantially increased anti-SARS-CoV-2 Spike S1 (S1) antibody concentrations in older persons against both the Wuhan and Omicron strains. Older age was associated with decreased antibody persistence both after the primary vaccination series and up to 1 year after the fifth vaccine dose. In infection-naïve persons the presence of inflammatory diseases was associated with an increased antibody response to the third vaccine dose (Beta = 1.53) but was also associated with reduced persistence over the 12 months following the fifth (bivalent) vaccine dose (Beta = -1.7). The presence of cardiovascular disease was associated with reduced antibody persistence following the primary vaccination series (Beta = -1.11), but this was no longer observed after bivalent vaccination.
Conclusion: Although older persons with comorbidities such as inflammatory and cardiovascular diseases responded well to SARS-CoV-2 booster vaccinations, they showed a reduced persistence of these responses. This might indicate that especially these more vulnerable older persons could benefit from repeated booster vaccinations.