Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein in noninfected subjects could inhibit, through the OAS mechanism, the response to new epitopes of SARS-CoV-2 after infection. The present study analyzes whether the memory antibody B cell response generated by mRNA vaccines against S protein can inhibit the primary antibody immune response to other SARS-CoV-2 antigens, such as nucleocapsid protein (N protein). SARS-CoV-2 primary infection in vaccinated healthcare workers (HCWs) produced significantly lower titers of anti-N antibodies than that in nonvaccinated HCWs: 5.7 (IQR 2.3-15.2) versus 12.2 (IQR 4.2-32.0), respectively ( ). Therefore, spike protein vaccine-induced immune imprinting (original antigenic sin) reduces N protein antibody response.

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys^® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.

COVID-19 appears to have a progression of three stages. The latter stage is characterized by a high level of cytokine release, which in turn triggers an uncontrolled reaction known as cytokine storm where mast cells are involved. The presence of anti-IgE antibodies against SARS-CoV-2 in this phase has been previously reported, suggesting an association with the severity of the disease. Our study aims to assess the prognostic significance of IgE antibodies against SARS-CoV-2 across a spectrum of clinical presentations, including individual with mild symptoms, hospitalized patients, and those who presented a critical progression. The study included 64 patients distributed into the following groups: 22 critically ill hospitalized individuals (Critical); 21 non-critical hospitalized patients (Severe); 21 mild symptomatic non-hospitalized cases (Mild); and 22 healthy blood donors with samples collected in October 2019. Anti-IgE antibodies against Spike (S) protein were detected using a homemade ELISA, where the plate was sensitized with the RBD of recombinant S protein. Among 64 SARS-CoV-2 infected patients, 28.1% tested positive for IgE isotype antibodies against S protein RBD, whose prevalence was similar across severity groups: Mild 23.8%, Severe 28.6%, and Critical 31.8% (p = 0.842). Patients with IgE response exhibited higher levels of LDH compared to non-IgE responders, with a 40% increase (p = 0.037), and a non-significantly higher tendency in other inflammatory markers. In SARS-CoV-2 infection, roughly a fourth of patients presented an IgE isotype response, regardless of disease severity, which is associated with higher levels of LDH.

The aim of this study was to validate the detection of anti-nucleocapsid protein (N protein) antibodies for the diagnosis of SARS-CoV-2 infection in light of the fact that most COVID-19 vaccines use the spike (S) protein as the antigen. Here, 3550 healthcare workers (HCWs) were enrolled from May 2020 (when no S protein vaccines were available). We defined SARS-CoV-2 infection if HCWs were found to be positive by RT-PCR or found to be positive in at least two different serological immunoassays. Serum samples from Biobanc I3PT-CERCA were analyzed by Roche Elecsys^® (N protein) and Vircell IgG (N and S proteins) immunoassays. Discordant samples were reanalyzed with other commercial immunoassays. Roche Elecsys^® showed the positivity of 539 (15.2%) HCWs, 664 (18.7%) were found to be positive by Vircell IgG immunoassays, and 164 samples (4.6%) showed discrepant results. According to our SARS-CoV-2 infection criteria, 563 HCWs had SARS-CoV-2 infection. The Roche Elecsys^® immunoassay has a sensitivity, specificity, accuracy, and concordance with the presence of infection of 94.7%, 99.8%, 99.3%, and 0.96, respectively. Similar results were observed in a validation cohort of vaccinated HCWs. We conclude that the Roche Elecsys^® SARS-CoV-2 N protein immunoassay demonstrated good performance in diagnosing previous SARS-CoV-2 infection in a large cohort of HCWs.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease marked by the production of autoantibodies (AAb) against citrullinated proteins/peptides (ACPA). The shared epitope (SE) in the HLA-DRB1 gene is a major genetic risk factor for RA and has been linked to ACPA production, particularly in individuals exposed to environmental triggers such as smoking. However, the role of the SE itself, especially in its citrullinated form, as a target of humoral immunity in RA remains underexplored. Methods: We analyzed autoantibodies against SE-containing peptides (SE-AAb) in 150 RA patients, 62 patients with psoriatic arthritis (PsA), and 204 healthy controls. HLA-DRB1 polymorphisms associated with the SE (QKRAA, QRRAA, RRRAA) were evaluated by PCR-SSO. IgG reactivity against native, citrullinated, and carbamylated SE peptides, in linear and cyclic conformations, was assessed using a custom ELISA. Results: SE-AAb were detected in RA patients with frequencies ranging from 26.0% to 45.3%, depending on peptide conformation and post-translational modification, with the highest positivity observed against citrullinated SE peptides. Antibodies against cyclated citrullinated SE peptides were present in 45.3% of RA patients, compared with 21.6% of healthy controls. PsA patients also showed SE-AAb positivity, with frequencies ranging from 17.7% to 35.5%, displaying a pattern largely similar to RA. No significant association was observed between SE-AAb positivity and SE genetic carriage, and SE-AAb presence was not associated with clinical features of RA. Conclusion: SE-AAb are present in RA patients, particularly against citrullinated SE peptides, but are not specific to RA, as similar reactivity is observed in PsA. The presence of these autoantibodies is independent of SE genetic carriage, suggesting that inflammatory conditions rather than genetic SE status may contribute to their generation. Further studies are needed to clarify the clinical relevance of SE-AAb in RA pathogenesis.