Higher plasma levels of thymosin-α1 are associated with a lower waning of humoral response after COVID-19 vaccination: an eight months follow-up study in a nursing home

Abstract

Background: Older people achieve lower levels of antibody titers than younger populations after Covid-19 vaccination and show a marked waning humoral immunity over time, likely due to the senescence of the immune system. Nevertheless, age-related predictive factors of the waning humoral immune response to the vaccine have been scarcely explored. In a cohort of residents and healthcare workers from a nursing home that had received two doses of the BNT162b2 vaccine, we measured specific anti-S antibodies one (T1), four (T4), and eight (T8) months after receiving the second dose. Thymic-related functional markers, including thymic output, relative telomere length, and plasma thymosin-α1 levels, as well as immune cellular subsets, and biochemical and inflammatory biomarkers, were determined at T1, and tested for their associations with the magnitude of the vaccine response (T1) and the durability of such response both, at the short- (T1-T4) and the long-term (T1-T8). We aimed to identify age-related factors potentially associated with the magnitude and persistence of specific anti-S immunoglobulin G (IgG)-antibodies after COVID-19 vaccination in older people.

Results: Participants (100% men, n = 98), were subdivided into three groups: young (< 50 years-old), middle-age (50-65 years-old), and older (≥65 years-old). Older participants achieved lower antibody titers at T1 and experienced higher decreases in both the short- and long-term. In the entire cohort, while the magnitude of the initial response was mainly associated with the levels of homocysteine [β (95% CI); - 0.155 (- 0.241 to - 0.068); p = 0.001], the durability of such response at both, the short-term and the long-term were predicted by the levels of thymosin-α1 [- 0.168 (- 0.305 to - 0.031); p = 0.017, and - 0.123 (- 0.212 to - 0.034); p = 0.008, respectively].

Conclusions: Higher plasma levels of thymosin-α1 were associated with a lower waning of anti-S IgG antibodies along the time. Our results suggest that plasma levels of thymosin-α1 could be used as a biomarker for predicting the durability of the responses after COVID-19 vaccination, possibly allowing to personalize the administration of vaccine boosters.

Keywords: Antibody waning; BNT162b2 vaccine; Immunesenescence; Inflammaging; Magnitude and persistence of humoral response; Nursing home; RTL; Sj/β-TRECs ratio; Thymic-function; Thymosin-α1.

Fig. 1

Age-related differences in the humoral response to the BNT162b2 vaccine. A Comparison of anti-S antibody titers between study groups at T1. Differences in anti-S IgG antibodies were maintained even when the two outliers from the young group (**) were excluded (p = 0.048). B Correlation between age and the log₁₀ of anti-S antibody titers at T1. p values < 0.05 were considered statistically significant

Fig. 2

Longitudinal dynamics of Anti-S antibody titers by age-groups. Follow-up of anti-S antibody titers between T1 (one month after the second dose), T4 (four months after the second dose) and T8 (eight months after the second dose) in A) Young, B) Middle-Age and C) Older groups. For all comparisons, p values 0.05 were considered statistically significant. Friedman test p < 0.001 for all comparisons

Fig. 3

Factors associated with the magnitude and loss of anti-S titers after BNT162b2 vaccination. Spearman’s correlation analysis between potential age-related factors associated to the magnitude of the initial response to the vaccine (T1, one month after the second dose of the vaccine), as well as to the short-term loss (between T1 and T4) and to the long-term loss (between T1 and T8). Color intensity of boxes represents Spearman’s rank correlation coefficient value as indicated in the color legend. All colored boxes represent statistically significant correlations (p values < 0.05). * p values between 0.1 and 0.05