ABSTRACT
Background: In spring 2020, at the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Europe, we set up an assay system for large-scale testing of virus-specific and neutralising antibodies including their longevity. Methods: We analysed the sera of 1655 adult employees for SARS-CoV-2-specific antibodies using the S1 subunit of the spike protein of SARS-CoV-2. Sera containing S1-reactive antibodies were further evaluated for receptor-binding domain (RBD)- and nucleocapsid protein (NCP)-specific antibodies in relation to the neutralisation test (NT) results at three time points over six months. Results: We detect immunoglobulin G (IgG) and/or IgA antibodies reactive to the S1 protein in 10.15% (n = 168) of the participants. In total, 0.97% (n = 16) are positive for S1-IgG, 0.91% (n = 15) were S1-IgG- borderline and 8.28% (n = 137) exhibit only S1-IgA antibodies. Of the 168 S1-reactive sera, 8.33% (n = 14) have detectable RBD-specific antibodies and 6.55% (n = 11) NCP-specific antibodies. The latter correlates with NTs (kappa coefficient = 0.8660) but start to decline after 3 months. RBD-specific antibodies correlate most closely with the NT (kappa = 0.9448) and only these antibodies are stable for up to six months. All participants with virus-neutralising antibodies report symptoms, of which anosmia and/or dysgeusia correlate most closely with the detection of virus-neutralising antibodies. Conclusions: RBD-specific antibodies are most reliably detected post-infection, independent of the number/severity of symptoms, and correlate with neutralising antibodies at least for six months. They thus qualify best for large-scale seroepidemiological evaluation of both antibody reactivity and virus neutralisation.
ABSTRACT
Obesity has dramatically increased over the last 30 years and reaches according to World Health Organization dimensions of a global epidemic. The obesity-associated chronic low-level inflammation contributes to severe comorbidities and directly affects many immune cells leading to immune dysfunction and increased susceptibility to infections. Thus, prophylaxis against vaccine-preventable diseases is crucial, yet the responsiveness to several vaccines is unclear under obesity. In order to assess the responsiveness to tick-borne encephalitis (TBE) vaccine, we revaccinated 37 obese individuals and 36 normal-weight controls with a licensed TBE vaccine. Metabolic, hormonal, and immunologic profiles along with vaccine-specific humoral and cellular immune responses were evaluated in sera and peripheral blood mononuclear cells (PBMCs) before, 1 week, 4 weeks, and 6 months after TBE booster. Obese adults had significantly increased metabolic (triglycerides, cholesterol ratios, leptin, insulin) and proinflammatory (C-reactive protein) parameters. They showed stronger initial increase of TBE-specific Ab titers (d7_d28) followed by a significantly faster decline after 6 months, which correlated with high body mass index and leptin and insulin levels. The fold increase of Ab-titer levels was significantly higher in obese compared to control males and linked to reduced testosterone levels. Obesity also affected cellular responses: PBMCs of the obese vaccinees had elevated interleukin 2 and interferon γ levels upon antigen stimulation, indicating a leptin-dependent proinflammatory TH1 polarization. The expansion of total and naive B cells in obese might explain the initial increase of Ab titers, whereas the reduced B-memory cell and plasma blast generation could be related to fast Ab decline with a limited maintenance of titers. Among T follicular helper cell (Tfh) cells, the Tfh17 subset was significantly expanded particularly in obese males, where we observed a strong initial Ab increase. Systemic but not local vaccine side effects were more frequent in obese subjects as a possible consequence of their low-grade proinflammatory state. In summary, TBE booster vaccination was effective in obese individuals, yet the faster Ab decline could result in a reduced long-term protection. The sex-based differences in vaccine responses indicate a complex interplay of the endocrine, metabolic, and immune system during obesity. Further studies on the long-term protection after vaccination are ongoing, and also evaluation of primary vaccination against TBE in obese individuals is planned. Clinical Trial Registration: NCT04017052; https://clinicaltrials.gov/ct2/show/NCT04017052.