Search Results (332)

Background/Objectives: The SARS-CoV-2 pandemic challenged patients with inflammatory bowel disease (IBD) under immunosuppressive therapies. We used data from the RisCoin cohort to investigate factors associated with a poor immune response to mRNA vaccination in these patients. Methods: From 4115 RisCoin participants, we matched 110 IBD patients by age and time interval since the second mRNA vaccination with 306 healthcare workers (HCW) without comorbidities (HCW-healthy) and 292 with medical conditions (HCW-plus); all were SARS-CoV-2 infection naïve. Basic questionnaires collected data on medication, COVID-19 vaccinations and side-effects, dietary patterns, lifestyle factors, and self-perceived stress. Main outcomes included anti-spike immunoglobulin levels and antibody-mediated live-virus neutralization immunity (NT) to the Omicron BA.1 variant (threshold NT ≥ 10 defined as IC50 values ≥1:10 serum dilution) after the second (baseline) and third vaccinations. Results: At baseline, IBD patients treated with anti-TNF but not those under vedolizumab or ustekinumab therapy had lower anti-spike levels compared to HCW-healthy and HCW-plus (166 versus 1384 and 1258 BAU/mL, respectively; p < 0.0001). Anti-TNF compared to vedolizumab/ustekinumab-treated patients reached NT titers above threshold in 17% versus 64%, respectively, and HCW-subgroups in 73% and 79% (all p < 0.0001). Current smokers showed a four to five times increased risk for non-neutralizing immunity compared to non-smokers. After the third vaccination, NT titers did not reach threshold in 15% anti-TNF compared to 5% vedolizumab/ustekinumab-treated patients and none of HCW (p < 0.01). Patients with IBD reported fewer clinical symptoms after vaccination. Perceived stress was not increased. Conclusions: Our findings support individualized schedules for mRNA-based vaccines in IBD patients with different immunosuppressive therapies and enforcement of non-smoking. Full article

Background/Objectives: This study examines the longitudinal dynamics of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibody responses to SARS-CoV-2 infection and mRNA vaccination based on 81,878 serum samples from 23,616 healthcare workers (HCWs) across five European countries. It includes data across four scheduled vaccine doses—predominantly BNT162b2—with 25% of samples originating from individuals with confirmed prior infection, as evidenced by elevated anti-S levels, positive Anti-N antibodies, or PCR results. Methods: The study employed a shifted transformation method for data normalization and utilized the Bass diffusion model to predict antibody titer dynamics influenced by both internal factors—such as immune activation contextualized through sociodemographic issues—and external factors, including infection and vaccination. Despite the absence of direct measurements for some internal variables, the model effectively inferred their impact, enabling a rigorous and nuanced delineation of immune response profiles. Results: The Bass diffusion model rigorously captured variations in antibody titers, analyzed through demographic factors such as gender, age, and job role, while thoroughly accounting for pre-infection status. The results indicate that Anti-N antibodies, exclusively produced post-infection, exhibited a rapid decline, while anti-S antibodies, generated from both infection and vaccination, demonstrated prolonged persistence. A significant decline in anti-S levels was observed 3–5 months post-vaccination, with adaptive immunity—characterized by the dominance of internal factors effects relative to external ones—achieved in most groups after the fourth dose. However, adaptive immunity post second dose was limited to specific demographics. Conclusions: These findings emphasize the significance of the Bass Method in predicting vaccine-induced, hybrid immune responses and detecting adaptive immunity by overcoming limitations in internal factor data, thereby advancing effective vaccination and infection control strategies during public health crises. These findings highlight the Bass Method’s value in predicting vaccine-induced and hybrid immunity, effectively addressing internal factor data gaps to enhance vaccination and infection control strategies. Full article

Background/Objectives: Patients suffering from inflammatory bowel diseases (IBDs) undergoing treatment with anti-TNF antibodies mount a diminished humoral immune response to vaccination against SARS-CoV-2 compared to healthy controls. The characterization of variant-specific immune responses is particularly warranted among immunosuppressed patients, where reduced responses may necessitate further medical interventions. Methods: This pilot study investigated the humoral immune response of vaccinated IBD patients on anti-TNF medication and a comparable group of healthy individuals against the viral variants Alpha, Beta, Gamma, Delta, and Omicron BA.1 and BA.5. While total IgG antibodies targeting the receptor binding site of the spike protein of SARS-CoV-2 were quantified using a chemiluminescence microparticle immunoassay (CMIA), their potential neutralizing capacity was determined using commercial and variant-specific in-house surrogate virus neutralization tests (sVNTs) against a variant-specific in-house VSV-pseudotyped virus neutralization test (pVNT) as the gold standard. Results: Employing variant-specific assays recapitulated the immune escape functions of virus variants. Conspicuously, antibody reactivity against Alpha and Omicron BA.1 and BA.5 was strikingly poor in IBD patient sera post-initial vaccination compared to healthy individuals. A comparison of the diagnostic performance of assays with the pVNT revealed that identification of patients with inadequate humoral responses by CMIA and sVNT may require adjustments to cut-off values and end-point titration of sera. Following adaptation of cut-off values, patient sera exhibited reduced reactivity against all tested variants. The assay panel used substantiated the impact of anti-TNF therapy in IBD patients as to reduced strength, function, and breadth of the immune response to several SARS-CoV-2 variants. The immune response measured following the second vaccination was comparable to the antibody response observed in healthy individuals following the first vaccination. Conclusion: Variant-specific sVNTs and pVNTs have the potential to serve as valuable tools for evaluating the efficacy of adapted vaccines and to inform clinical interventions in the care of immunosuppressed patients. Anti-TNF-treated individuals with antibody levels below the optimized CMIA threshold should be considered for early booster vaccination and/or close immunological monitoring. Full article

Background/Objectives: Severe acute respiratory syndrome (SARS-CoV-2) has had a profound global impact and continues to represent a health challenge worldwide. The durability of SARS-CoV-2 vaccine responses in pediatric inflammatory bowel disease (PIBD) patients receiving biologic therapies is unknown. This study aimed to quantify SARS-CoV-2 antibody responses post vaccination in these immunosuppressed patients over 12 months. Methods: Prospective study comparing antibody responses against SARS-CoV-2 spike protein at 1, 3, 6, and 12 months in PIBD patients aged 5–18 years treated with anti-tumor necrosis factor alpha (anti-TNF) therapies with or without an immunomodulator (IM) versus vedolizumab. Results: Between 1 May 2021 and 1 May 2022, 194 participants on anti-TNF monotherapy (n = 78), anti-TNF with IM (n = 83), vedolizumab (n = 15), and steroids (n = 18) were recruited. Anti-SARS-CoV-2 spike levels increased after the first vaccine and were further boosted 1 month after the second dose. Linear mixed-effects modelling showed antibody waning over time (effect difference −2509 IgG AU/mL per week [95%CI: −4998–−20, p = 0.048]), counterbalanced by booster doses (effect difference 184,138 IgG AU/mL per additional vaccine dose [95%CI: 138,342–229,934, p < 0.001]). Receiving anti-TNF therapy contributed to reduced antibody responses compared to vedolizumab (anti-TNF monotherapy effect difference: −212,640 [95%CI: −336,928–−88,351] p = 0.001; anti-TNF with IM: −151,880 [95%CI: −277,309–−26,451] p = 0.018). Seroconversion and breakthrough infection rates were similar between groups, and all infections were mild, without hospitalizations. Conclusions: Although SARS-CoV-2 antibody responses were attenuated in PIBD patients receiving anti-TNF therapy compared with vedolizumab, this did not impact protection, as seroconversion and breakthrough infection rates were similar, with no hospitalizations. These data reinforce the importance of updating vaccines and, in particular, SARS-CoV-2 vaccines in immunosuppressed PIBD patients on advanced therapies. Full article

Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization and mortality rates in the general population and ESKD patients. Neutralizing antibodies (NAbs) are a valuable correlate of protection after vaccination, and IgG anti-spike antibodies are considered a surrogate marker of protection. Methods: This study investigated the correlates of protection brought by NAb and anti-spike IgG antibodies against SARS-CoV-2 wild-type Wuhan strain and variants of concern in a cohort of 128 French patients on dialysis after vaccination with the BNT162b2 mRNA vaccine. The correlate was assessed using Receiver Operating Characteristic curves. Results: The level of protection for IgG anti-spike antibodies was set at 917 BAU/mL for the original Wuhan strain and 980 BAU/mL and 1450 BAU/mL, respectively, for the Delta and Omicron BA.1 variants. Conclusions: The level of protection can be regularly monitored by measuring IgG anti-spike antibody concentrations to allow tailored boosters of SARS-CoV-2 vaccination in this frail and immunocompromised ESKD population. Full article

The SARS-CoV-2 virus poses a significant risk to immunocompromised patients, who display weakened immunity and reduced seroconversion following infection and vaccination. In this study, we recruited 19 hospitalized patients with immune disorders (ImCo) and 4 immunocompetent controls (ICC) with COVID-19. We evaluated their serological, humoral, and cellular immune responses at <30 days and >90 days post-symptom onset. ICC patients showed robust B and T cell responses against SARS-CoV-2, indicated by detectable antibody levels, memory antibody-secreting cells (mASCs) towards the spike protein and spike-specific CD4⁺ and CD8⁺ T cells. ImCo patients showed impaired immune responses, with lower levels of B cell responses. Further subdivision of the ImCo patients demonstrates that solid organ transplant (SOT) patients generated B cell responses similar to ICC patients, whereas the other ImCo patients, including patients with hematological malignancies and anti-CD20 therapy, did not. Absolute T cell numbers and spike-specific CD4⁺ and CD8⁺ T cell responses were low in the ImCo patients at <30 days but increased at later time points. Our findings suggest that even when B cell responses were reduced, patients could present a T cell response, suggesting a more successful line of passive immunization for immunocompromised individuals focusing on boosting T cell responses. Full article

mRNA vaccines have demonstrated considerable efficacy and safety against SARS-CoV-2, limiting the pandemic burden worldwide. The emergence of new variants of concern and the decline in neutralizing activity observed several weeks post-vaccination reinforced the call for repeated mRNA vaccination. We and others have shown that vaccine efficacy does not exclusively rely on antibody neutralizing activites; Fc-effector functions play an important role as well. However, it is well known that long-term exposure and repeated antigen stimulation elicit the IgG4 subclass of antibodies, which are inefficient at mediating Fc-effector functions. In this regard, recent studies highlighted concerns about IgG4 induction by mRNA vaccines. Here, we explored the impact of repeated mRNA vaccination on IgG4 induction and its impact on Fc-effector functions. We observed anti-Spike IgG4 elicitation after three doses of mRNA vaccine; the antibody levels further increased with additional doses. Vaccine-elicited IgG4 preferentially bound the ancestral D614G Spike. We also observed that Breakthrough Infection (BTI) after several doses of vaccine strongly increased IgG1 levels but had no impact on IgG4 levels, thereby improving Fc-effector functions. Finally, we observed that elderly donors vaccinated with Moderna mRNA vaccines elicited higher IgG4 levels and presented lower Fc-effector functions than donors vaccinated with the Pfizer mRNA vaccine. Altogether, our results highlight the importance of monitoring the IgG subclasses elicited by vaccination. Full article

SARS-CoV-2 has caused global disruptions, prompting studies on immune responses to COVID-19 vaccines, particularly antibodies against the Spike (S) protein. However, responses to the Nucleocapsid (N) protein remain less explored. This study evaluated whether CoronaVac induces anti-N antibodies, and analyzed antibody dynamics after a BNT162b2 booster, given that CoronaVac targets both S and N proteins, while BNT162b2 targets only the S protein. Serum samples were collected at multiple intervals post-vaccination. The percentage of participants with positive anti-N antibodies increased from 40.26% to 62.09% after two doses of CoronaVac, but declined over time, reaching 29.07% and 18.87% after the second and third doses, respectively. However, seropositivity rose to 43.48% three months after the booster. Anti-S antibody levels peaked at 31,394 AU/mL after the booster, compared to 723.4 AU/mL after the first dose. These findings indicate that CoronaVac stimulates antibody responses against both S and N proteins. Monitoring antibody dynamics is crucial for optimizing vaccination strategies, particularly for high-risk populations, to help control COVID-19. Full article

Background/Objectives: The aim of our study was to investigate B cell and T cell responses in people with multiple sclerosis (PwMS) treated with ocrelizumab, a humanized anti-CD20 antibody, who were vaccinated with second and/or booster doses of various vaccine brands against COVID-19. Additionally, we detected the outcomes related to COVID-19 in PwMS after vaccination, based on follow-up for at least 12 months. Methods: We enrolled 91 PwMS on ocrelizumab and 42 healthy controls (HCs) in a prospective, single-center study, conducted at the Clinic of Neurology, UCCS, between January 2022 and October 2024. The serological responses were measured using the spike receptor-binding domain (RBD) Architect SARS-CoV-2 IgG Quant kit (Abbot), and cellular responses were measured by quantifying IFN-γ secretion in blood incubated with SARS-CoV-2 antigens. Results: A total of 58.2% (53/91) of PwMS on ocrelizumab and 100% of the HCs (42/42) were seropositive after a second or booster vaccination (p < 0.001), irrespective of the vaccine brand received. Anti-spike antibody levels were significantly lower in PwMS on ocrelizumab compared to the HCs (p < 0.001), again irrespective of the vaccine type. Interferon-γ responses were detected in 95.6% of the PwMS receiving ocrelizumab therapy and 97.6% of HCs after vaccination (p = 0.570). In our cohort, PCR-confirmed SARS-CoV-2 infections after vaccination occurred in a similar proportion of the PwMS (45/91, 49.5%) and HCs (15/32, 46.9%) (p = 0.139). Most of the PwMS (36/45, 79.2%) and HCs (13/15, 87.8%) had COVID-19 of mild severity. Conclusions: PwMS treated with ocrelizumab developed diminished humoral and robust cellular responses following two and three SARS-CoV-2 vaccinations. The obtained immunity after SARS-CoV-2 vaccination may translate into lower incidence and severity of COVID-19. Full article

An increase in immunoglobulin G4 (IgG4) levels is typically associated with immunological tolerance states and develops after prolonged exposure to antigens. Accordingly, IgG4 is considered an anti-inflammatory antibody with a limited ability to trigger efficient immune responses. Additionally, IgG4 reduces allergic reactions by blocking immunoglobulin E (IgE) activity. In the case of COVID-19, it has been reported that the repeated administration of some vaccines induces high IgG4 levels. The latest research data have revealed a surprising IgE anti-receptor binding domain response after both natural infection and several SARS-CoV-2 vaccines. The presence of IgG4 and IgE in COVID-19 disease suggests that the virus may induce an “allergic-like” response to evade immune surveillance, leading to a shift from T helper 1 (Th1) to T helper 2 (Th2) cells, which promotes tolerance to the virus and potentially contributes to chronic infection. The spike protein from vaccines could also induce such a response. Interestingly, “allergen-like” epitopes and IgE responses have been reported for other viruses, such as influenza, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV). The impact of this viral-induced tolerance will be discussed, concerning long COVID and the protective efficacy of vaccines. Full article

Background/Objectives: This study mapped antibody dynamics across three COVID-19 vaccination rounds (primary course, first, and second booster with BNT162b2) in Belgian nursing home residents (NHRs). Methods: Within a national SARS-CoV-2 serosurveillance study (February 2021–September 2022) across Belgian nursing homes, dried blood spots were collected, on which anti-spike SARS-CoV-2 IgG antibodies were quantified by ELISA in international units/mL (IU/mL). Sociodemographic data were collected at the study start and infection history and vaccination data at each sampling round. Results: Infection-naïve NHRs had low antibody levels after primary course vaccination (geometric mean concentration (GMC) 292 IU/mL, 95% confidence interval (95% CI): 197–432), but increased tenfold after first booster (GMC 2168 IU/mL, 95% CI: 1554–3027). While antibodies among NHRs significantly declined within six months after primary vaccination (p < 0.0001), they remained stable for nine months post-booster (p > 0.05). Among primary vaccine non-responders, 92% (95% CI: 82–97%) developed antibodies after the first booster (GMC 594 IU/mL, 95% CI: 416–849), though tenfold lower than initial responders (GMC 4642 IU/mL, 95% CI: 3577–6022). Conclusions: These findings demonstrate that NHRs require tailored vaccination, prioritizing repeated immunization to improve serological outcomes in poor responders such as infection-naive NHRs. Regular immune monitoring could aid in implementing evidence-based vaccine strategies, ensuring optimal protection for vulnerable populations against SARS-CoV-2 and other infectious threats. Full article

Background: The COVID-19 pandemic highlighted the vulnerability of immunocompromised individuals, including liver transplant recipients (LTRs), who often exhibit reduced vaccine immunogenicity. While initial vaccine doses and subsequent boosters improved immune response, LTRs were prioritized for vaccination. Studies have shown increased antibody response after each booster dose. Vaccine hesitancy, defined as delayed or refused vaccination despite availability, poses a public health challenge, often fueled by misinformation. This study aimed to evaluate anti-spike antibody responses in vaccinated LTRs after two initial doses and at least one booster, also assessing adherence to subsequent doses. Methods: We conducted a retrospective observational study at a transplant center in Milan, Italy, between January 2021 and December 2023. LTRs who had received four or more doses of mRNA vaccines (Pfizer or Moderna) were included. Anti-spike antibody levels were measured 60–80 days after each dose. Data on vaccination status were collected in January 2024. Statistical analysis was performed to compare antibody responses and identify predictive factors. Results: LTRs showed a significant increase in anti-spike antibody responses after the first booster compared to the second dose with a trend versus a further increase following the fourth dose in a subgroup of the patients receiving two booster doses. However, adherence to booster doses decreased over time. In LTRs, predictors of a weaker response after the second dose were chronic kidney disease and metabolic etiology at transplant. Conclusions: The study highlighted that in LTRs, multiple doses of the COVID-19 vaccine led to a continuous increase in anti-spike antibody responses. The progressive decline in adherence of LTRs “to further booster doses” should be related to the fact that after the spread of vaccination programs worldwide, COVID-19 is still a current infection, but it is much less severe than before. Full article

Disease-modifying therapies (DMTs) are known to impact cellular and humoral immune response in persons with multiple sclerosis (pwMS). In this study, we performed in-depth SARS-CoV-2-specific T-cell profiling using flow cytometry. T-cell immunity in pwMS with or without DMTs was evaluated before a first SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccination and at one-, two- and six-month follow-up. T-cell stimulation without SARS-CoV-2-specific antigens was used as a control. T-cell response was compared to B-cell response by evaluating SARS-CoV-2-specific antibodies. We observed an upregulation of specific subpopulations of SARS-CoV-2 spike-specific CD4⁺ T cells. Thus, our results demonstrate the induction of a broad and distinct CD4⁺ T-cell response in pwMS even on anti-CD20 treatment and sphingosine-1-phosphate receptor modulation after SARS-CoV-2 mRNA vaccination. This was particularly seen in CD4^+high and CD4⁺CD154⁺ T cells. Our results do not support the induction of a CD8⁺ T-cell immune response. While humoral immune response was impaired in pwMS during ocrelizumab and fingolimod treatment, there was evidence of a compensatory upregulation of subpopulations of SARS-CoV-2-specific CD4⁺ T cells at low levels of seroconversion in pwMS. In conclusion, our results provide important insights into the mechanisms of the adaptive immune response in pwMS following SARS-CoV-2 mRNA vaccination. Full article

This study investigates the impact of immunological and clinical factors on COVID-19 outcomes among unvaccinated individuals. A cohort of 42 unvaccinated patients admitted to an intensive care unit was analyzed, focusing on age, comorbidities, inflammatory cytokines (IL-6, TNF-α), and anti-SARS-CoV-2 spike protein antibody levels (IgG) to assess their influence on hospital stay duration, recovery time, complications, and mortality rates. The findings revealed that advanced age, cardiovascular disease, and elevated pro-inflammatory cytokines significantly heightened the risks of severe complications and mortality. Conversely, low IgG levels correlated with prolonged hospital stays and slower recovery. Multivariate analysis identified high IL-6 and TNF-α levels as strong predictors of adverse outcomes. This research emphasizes the need for the early monitoring of cytokines and targeted management strategies to mitigate the impact of COVID-19, especially among high-risk unvaccinated populations. Full article

Background/Objectives: Novel mRNA vaccines have been successfully utilized to curtail the SARS-CoV-2 pandemic. However, the immunology underlying CoV2 vaccinations, particularly with repeated boosting, has not been properly characterized due to limitations in the preclinical modeling of SARS-CoV-2 infection/vaccinations as well as constantly changing vaccine formulations. The immunoregulatory aspects involved in such vaccine approaches remain unclear. Antibodies, due to inherent immunogenicity by VDJ gene rearrangement, have the potential to induce antibodies directed towards them called anti-idiotype antibodies, which can play a downregulatory role in responses. The paratope of some of these anti-idiotype antibodies can also act as a mirror to the original antigen, which, in the case of SARS-CoV-2 vaccines, would be to the spike protein and, therefore, also be capable of binding its target, ACE2, potentially causing adverse effects. Methods: To investigate if sequential SARS-CoV-2 mRNA vaccination can induce anti-idiotype antibody responses, K18 hACE2 transgenic mice were serially vaccinated with a SARS-CoV-2 mRNA construct to determine the kinetics of anti-spike and anti-ACE2 responses via custom-made ELISAs. Results: While sequential vaccination produced robust anti-spike responses, anti-ACE2 levels were also detected and gradually amplified with each boost. These anti-ACE2 antibodies persisted for 3 months after the final vaccination and showed evidence of hACE2 binding, as levels were lower in K18 mice in comparison to the wild type. Conclusions: These data would suggest that sequential SARS-CoV-2 mRNA vaccination has the potential to induce anti-ACE2 antibodies in mice, with each boost amplifying the amount of antibody. Full article