Association of total and neutralizing SARS-CoV-2 spike -receptor binding domain antibodies with epidemiological and clinical characteristics after immunization with the 1st and 2nd doses of the BNT162b2 vaccine

Abstract

Background Data regarding the association of antibody levels elicited after immunization with the BNT162b2 mRNA Covid-19 vaccine with epidemiological and clinical parameters are limited. Methods We prospectively measured the total (TAbs-RBD) and the neutralizing antibodies (NAbs-RBD) against the receptor binding domain (RBD) of SARS-CoV-2 spike protein in a cohort of 268 Healthcare workers before immunization, 20 days after the 1 st dose and 30 days after the 2 nd dose of the BNT162b2 vaccine. A statistical analysis for possible association of antibodies’ levels with epidemiological and clinical parameters was performed. Results The mean age (±SD) of the participants was 45.45 years (± 11.93) (range: 24-70 years) and 211 (79.9%) were females. Statistically significant differences were detected regarding both TAbs-RBD and NAbs-RBD between the first and second doses of the vaccine (P<0.001). The median (IQR) percentage (%) of NAbs-RBD after the 1 st dose was 51.07% (31.60%) and after the 2 nd dose 95.31% (3.70%) (P<0.001).The correlation between the TAbs-RBD and NAbs-RBD was after the 1 st dose, Spearman’s, rho: 0.861 ( P <0.001) and after the 2 nd dose rho: 0.989 ( P <0.001). Twenty days after the 1 st dose, 56/264 (21.2%) of the participants did not have detectable NAbs-RBD, while one month after the 2 nd dose all of them had detectable NAbs-RBD. After the 2 nd vaccine dose, a statistically significant negative association of TAbs-RBD was detected for age (P<0.001), smoking ( P =0.011), and immunosuppressive medications (P<0.001), while a positive association was detected for BMI (P=0.004) and systemic adverse events after immunization (P=0.001). Conclusion A significant correlation of TAbs-RBD and NAbs-RBD was detected after both vaccine doses. Older age, smoking, and immunosuppressive medications negatively affected the final antibody level after SARS-CoV-2 immunization. Our findings emphasize the significance of the 2 nd vaccine dose especially in the older age groups.

The Effect of Smoking on Humoral Response to COVID-19 Vaccines: A Systematic Review of Epidemiological Studies

“…Another report did not specify the enrolled population. In 17 out of 23 studies, current smokers showed significant lower antibody titre, and in a few reports, highlighted a more rapid lowering of the vaccine-elicited IgG compared with nonsmokers [19,20,[26][27][28][29][30]32,34,[36][37][38][39][40][41]43,44]. In particular, accelerated antibody decline was reported in the prospective assessments by Ferrara et al [20], Zhang et al [27], and Malavazos et al [30].…”

Long-term decay of anti-RBD IgG titers after BNT162b2 vaccination is not mirrored by loss of neutralizing bioactivity against SARS-CoV-2

“…Immunogenicity of vaccines can be evaluated through different serum and cellular markers that exhibit a range of kinetics and evolutions over time. It became evident early on through the pandemic that neutralizing activity is highly correlated with anti-RBD IgG values [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] but an absolute conversion factor could not be established. That may in part be due to major inter-studies heterogeneity as to the kind of patients (COVID-19 experienced vs. COVID-19 naive), immune binding assays and neutralization assays that were implemented, making comparisons unreliable, in part to apparent divergent kinetics of neutralizing and anti-RBD Abs that some studies highlighted [16] , [22] , [35] , [36] .…”

“…While quantitative binding assays only identify physical interactions and are mainly used for diagnostic purposes, functional neutralizing activity can only be directly investigated by means of VNTs platforms, that are grossly divided into direct VNTs, which require viable virions of SARS-CoV-2 and are considered the gold standard, and surrogate (s)VNTs, based on binding competition assays between antibodies and target receptors that mediate viral attachment and entry. Studies available so far have shown a significant degree of correlation between anti-S-RBD Abs levels and serum neutralizing bioactivity as assessed by VNTs [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , nonetheless some other studies have remarked that this correlation might change over time due to affinity maturation of humoral response, thus limiting the absolute quantitative value of anti-S-RBD Abs as a reliable COP [15] , [16] , [22] , [23] , [24] , [25] , [26] . In fact, waning of binding Abs either after natural infection or vaccination might be countered by the maintenance of neutralizing capacity by ongoing affinity maturation of Spike-specific B lymphocytes [27] .…”

SARS-CoV-2 variants and effectiveness of vaccines: a review of current evidence

“…74 Recent studies have shown there is association of immunological response and NAc of BNT162b2 vaccine with several epidemiological and clinical characteristics. 75,76 In addition, concerns have been raised regarding the impact of the emerging variants to the NAc and T-cell responses stimulated by the vaccine.…”

“…Both vaccines have been found to be highly effective in clinical trials as well as in mass vaccination programmes with tolerable reactogenicity [ 73 ]. Recent studies have shown that there is an association of immunological response and NAc of BNT162b2 vaccine with several epidemiological and clinical characteristics [ 74 , 75 ]. In addition, concerns have been raised regarding the impact of the emerging variants to the NAc and T-cell responses stimulated by the vaccine.…”