Specific Antibody Concentrations Research Articles

Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity.

The immunological mechanisms behind the clinical association between asthma and obesity in adolescence are not fully understood. This study aimed to find new plasma protein biomarkers associated specifically with coincident asthma and obesity in adolescents. This was a cross-sectional study in children and adolescents 10-19 years old (N = 390). Relative plasma concentrations of 113 protein biomarkers related to inflammation and immune response were determined by proximity extension assay (Target 96; Olink, Uppsala, Sweden). Differences in protein concentrations between healthy controls (n = 84), subjects with asthma (n = 138), subjects with obesity (n = 107), and subjects with both asthma and obesity (AO; n = 58) were analyzed by ANCOVA, adjusting for age and sex, and in a separate model adjusting also for the sum of specific IgE antibody concentrations to a mix of food allergens (fx5) and aeroallergens (Phadiatop). Proteins elevated in the AO group but not in the obesity or asthma groups were considered specifically elevated in asthma and obesity. Five proteins were elevated specifically in the AO group compared to controls (here sorted from largest to smallest effect of asthma and obesity combined): CCL8, IL-33, IL-17C, FGF-23, and CLEC7A. The effects of adjusting also for specific IgE were small but IL-33, IL-17C, and FGF-23 were no longer statistically significant. We identified several new potential plasma biomarkers specifically elevated in coincident asthma and obesity in adolescents. Four of the proteins, CCL8, IL-33, IL-17C, and CLEC7A, have previously been associated with viral mucosal host defense and Th17 cell differentiation.

Exploring the possible link between the spike protein immunoglobulin G4 antibodies and cancer progression

Repeated inoculation with messenger RNA (mRNA) vaccines elicits immunoglobulin G4 (IgG4) antibody production. Such an increase in the concentration of specific and non-specific IgG4 antibodies allows the growth of some types of cancer by blocking the activation of effector immune cells. This work proposes the hypothesis that cancer growth may be indirectly promoted by increased concentrations of non-specific IgG4 antibodies by the following mechanisms: 1) IgG4 antibodies can bind to anti-tumor IgG1 antibodies and block their interaction with receptors located on effector cells, thus preventing the destruction of cancer cells, 2) IgG4 can interact with fragment crystallizable gamma receptor IIb (FcγRIIB) inhibitory receptors, thus reducing effector functions of innate immune cells, and 3) targeting of specific epitopes by IgG4 could be oncogenic by inducing the production of a microenvironment that can promote cancer development. This article reviews the supporting literature and suggests several experimental protocols to evaluate this hypothesis in the context of repeated inoculation with mRNA vaccines. Additionally, this work proposes some management options aimed at reducing the unfavorable molecular consequences that could mediate cancer development when encountering high concentrations of IgG4 antibodies.

Adaptive immune responses to two-dose COVID-19 vaccine series in healthy Canadian adults ≥ 50 years: a prospective, observational cohort study

To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.

Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen.

The exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials. We conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d'Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p < .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline. No clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen. NCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov.

Enhancing Immune Response in Non-Small-Cell Lung Cancer Patients: Impact of the 13-Valent Pneumococcal Conjugate Vaccine.

Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients' and physicians' awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life.

Quantitative detection and prognostic value of antibodies against M-type phospholipase A2 receptor and its cysteine-rich ricin domain and C-type lectin domains 1 and 6-7-8 in patients with idiopathic membranous nephropathy.

M-type phospholipase A2 receptor (PLA2R) is the major autoantigen in adult idiopathic membranous nephropathy (IMN). Although reactive epitopes in the PLA2R domains have been identified, the clinical value of these domains recognized by anti-PLA2R antibodies remains controversial. Accordingly, this study aimed to quantitatively detect changes in the concentrations of different antibodies against epitopes of PLA2R in patients with IMN before and after treatment to evaluate the clinical value of epitope spreading. Highly sensitive time-resolved fluorescence immunoassay was used to quantitatively analyze the concentrations of specific IgG and IgG4 antibodies against PLA2R and its epitopes (CysR, CTLD1, CTLD6-7-8) in a cohort of 25 patients with PLA2R-associated membranous nephropathy (13 and 12 in the remission and non-remission groups, respectively) before and after treatment, and the results were analyzed in conjunction with clinical biochemical indicators. The concentration of specific IgG (IgG4) antibodies against PLA2R and its epitopes (CysR, CTLD1 and CTLD6-7-8) in non-remission group was higher than that in remission group. The multipliers of elevation of IgG (IgG4) antibody were 5.6(6.2) fold, 3.0(24.3) fold, 1.6(9.0) fold, and 4.2(2.6) fold in the non-remission/remission group, respectively. However, the difference in antibody concentrations between the two groups at the end of follow-up was 5.6 (85.2), 1.7 (13.1), 1.0 (5.1), and 1.5 (22.3) times higher, respectively. When detecting concentrations of specific IgG antibodies against PLA2R and its different epitopes, the remission rate was 66.67% for only one epitope at M0 and 36.36% for three epitopes at M0. When detecting concentrations of specific IgG4 antibodies against PLA2R and its different epitopes, the remission rate was 100.00% for only one epitope at M0 and 50.00% for three epitopes at M0. A trivariate logistic regression model for the combined detection of eGFR, anti-CTLD678 IgG4, and urinary protein had an AUC of 100.00%. Low concentrations of anti-CysR-IgG4, anti-CTLD1-IgG4, and anti-CTLD6-7-8-IgG4 at initial diagnosis predict rapid remission after treatment. The use of specific IgG4 against PLA2R and its different epitopes combined with eGFR and urinary protein provides a better assessment of the prognostic outcome of IMN.

Understanding hypergammaglobulinemia in experimental or natural visceral leishmaniasis.

Nonspecific hypergammaglobulinemia (HGG) occurs in symptomatic human visceral leishmaniasis (VL) caused by L. L. infantum. This study assessed this finding in experimental infection in hamsters and natural infection in dogs. The serum concentration of proteins, albumin and globulins was determined through the biuret and bromocresol green reaction, where the HGG was better expressed through the albumin/globulin (A/G) ratio. HGG was associated with a higher concentration of specific anti-glycan antibodies (BSA-G)/promastigote soluble extract (PSE) and the presence of circulating immune complexes (IC) by dissociative enzyme-linked immunoassay (ELISA). The study found monovalent IC in 37.9% (PSE) and 50% (BSA-G) of sera from infected hamsters, with increased frequency as the disease progressed. HGG was found in >60% of the samples in dogs with VL, associated with higher levels of specific immunoglobulin (Ig)A and IgM, but not IgG, determined using the PSE and BSA-G ELISA. HGG was associated with the presence of monovalent IC in 58.9% (PSE) and 63.4% (BSA-G) positive dog samples. HGG may result not only from the nonspecific activation of B cells, with greater production of specific and nonspecific antibodies, but also due to lower IgG excretion due to the presence of soluble monovalent IC. HGG correlates to the progression of VL and may be a marker for manifested disease.

The impact of elevated lipoprotein a levels on retinal vein occlusion in young individual: Case report with 7 months follow‐up

Aims/Purpose: Branch retinal vein occlusion (BRVO) occurs when a branch of the retinal vein becomes obstructed. The aim of this study case was to provide insights into the potential role of Lipoprotein (Lp) (a) in the pathogenesis of BRVO.Methods: Case of a 47‐year‐old woman with no significant ophthalmological or general medical history, except the use of oral contraception and smoking habits. Presented to the emergency care after 5 days of experiencing a sudden vision loss in her right eye.Results: The ophthalmological examination revealed a visual acuity of 10/10 on the left (OS) and VBLM/10 on the right eye (OD). Slit lamp and Fundus examination showed on OD a relative afferent pupillary defect and the classic features of acute retinal branch vein occlusion, including tortuous veins, capillary occlusion, papillary and macular oedema and haemorrhages. While all was normal in OS. A comprehensive ophthalmic examination was conducted, including fluorescein angiography and optical coherent tomography that showed no abnormal vessel growth at this stage. Then, the indication for a dexamethasone intravitreal implant has been made along with panretinal photocoagulation (PRP) in the ischaemic areas. More, discontinuing oral contraception, the serum concentrations of specific antibodies, as anticardiolipin and antiphospholipids, as well as homocysteine and Lp (a) levels. The blood tests yielded negative results except for the abnormal plasma level of lipoprotein (a), which was measured at 900 mg/L. After 2 months of follow‐up. The visual acuity in OD was measured at 9/10. Moreover, the restoration of normal macular thickness after 4 months. However, at 6 months follow‐up, the appearance of a neovascularization adjacent to the previously laser‐treated area. As a result, a series of closely spaced PRP was performed along with an intravitreal anti‐vascular endothelial growth factor. After 1 month, a complete disappearance of the neovascularization was observed.Conclusions: Identification of independent and highly predictive risk factors for BRVO is still a big challenge. The main goals are the preservation of visual acuity and the prevention of relapses. This case report emphasizes the importance of incorporating a systematic Lp (a) testing into clinical practice, even in young individual.

Enhanced Lateral Flow Immunoassay with Double Competition and Two Kinds of Nanoparticles Conjugates for Control of Insecticide Imidacloprid in Honey.

Finding optimal conditions for competitive lateral flow immunoassay is a controversial task. The content of specific antibodies labeled by nanoparticles should be simultaneously high to reach intense signals and low to register an influence on the signals for minimal concentrations of the target analyte. We propose to use two kinds of complexes of gold nanoparticles in the assay, with antigen-protein conjugates and with specific antibodies. The first complex interacts both with immobilized antibodies in the test zone and with antibodies on the surface of the second complex. In this assay, the coloration is enhanced by the binding of two-colored preparations in the test zone, whereas the antigen in the sample inhibits both the binding of the first conjugate with the immobilized antibodies and with the second conjugate. This approach is realized for the detection of insecticide imidacloprid (IMD), an important toxic contaminant connected with the recent global death of bees. The proposed technique expands the working range of the assay, that is, in accordance with its theoretical analysis. The reliable change of coloration intensity is achieved for a 2.3-times-lower concentration of the analyte. The limit of IMD detection is 0.13 ng/mL for tested solutions and 1.2 µg/kg for initial honey samples. The combination of two conjugates doubles the coloration in the absence of the analyte. The developed lateral flow immunoassay is applicable for five-fold-diluted honey samples without extraction, does not require additional stages (all reagents are pre-applied to the test strip), and is implemented in 10 min.

PRIMING OF CHIKENS WITH LIVE AND INACTIVATED IBС VACCINE

The research gives the results of the experiments to study the effect of priming the chickens with a live and inactivated vaccine against the IBC virus, and subsequent immunization with a live vaccine. The research demonstrates the results of the study of optimal schemes of birds’ immunization with live and inactivated vaccines, when the greatest specific effect is achieved.&#x0D; It has been established that priming chickens that do not contain antibodies against IBC with both live and inactivated vaccines causes the formation of intense immunity in them, which indicates a mature immune system capable of actively responding to a foreign antigen in the first days of life.&#x0D; Priming chickens with a live vaccine based on the background of maternal antibodies is not accompanied by the synthesis of antibodies, unlike priming with an inactivated vaccine, which leads to the formation of insignificant humoral immunity.&#x0D; Vaccination chickens containing maternal antibodies with live vaccine, primed with both live and inactivated vaccine depends on the content of specific antibodies in their body and is more effective when the level of antibodies in their body is low.

Early detection of lung cancer in a real-world cohort via tumor-associated immune autoantibody and imaging combination.

Efficient early detection methods for lung cancer can significantly decrease patient mortality. One promising approach is the use of tumor-associated autoantibodies (TAABs) as a diagnostic tool. In this study, the researchers aimed to evaluate the potential of seven TAABs in detecting lung cancer within a population undergoing routine health examinations. The results of this study could provide valuable insights into the utility of TAABs for lung cancer screening and diagnosis. In this study, the serum concentrations of specific antibodies were measured using enzyme-linked immunosorbent assay (ELISA) in a cohort of 15,430 subjects. The efficacy of both a 7-TAAB panel and LDCT for lung cancer detection were evaluated through receiver operating characteristic (ROC) analyses, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) being assessed and compared. These results could have significant implications for the development of improved screening methods for lung cancer. Over the 12-month observation period, 26 individuals were diagnosed with lung cancer. The 7-TAAB panel demonstrated promising sensitivity (61.5%) and a high degree of specificity (88.5%). The panel's area under the receiver operating characteristic (ROC) curve was 0.8062, which was superior to that of any individual TAAB. In stage I patients, the sensitivity of the panel was 50%. In our cohort, there was no gender or age bias observed. This 7-TAAB panel showed a sensitivity of approximately 60% in detecting lung cancer, regardless of histological subtype or lesion size. Notably, ground-glass nodules had a higher diagnostic rate than solid nodules (83.3% vs. 36.4%, P = 0.021). The ROC analyses further revealed that the combination of LDCT with the 7-TAAB assay exhibited a significantly superior diagnostic efficacy than LDCT alone. In the context of the study, it was demonstrated that the 7-TAAB panel showed improved detective efficacy of LDCT, thus serving as an effective aid for the detection of lung cancer in real-world scenarios.

Antibody Assay and Anti-Inflammatory Function Evaluation of Therapeutic Potential of Different Intravenous Immunoglobulins for Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease that currently has no known cure. Intravenous immunoglobulin (IVIG), which contains AD-related antibodies and has anti-inflammatory properties, has shown potential as a treatment for AD. However, the efficacy of clinical trials involving AD patients treated with IVIG has been inconsistent. Our previous study found that different IVIGs had significantly varied therapeutic effects on 3xTg-AD mice. In order to investigate the relationship between the composition and function of IVIG and its efficacy in treating AD, we selected three IVIGs that showed notable differences in therapeutic effects. Then, the concentrations of specific antibodies against β-amyloid (Aβ)42, tau, and hyperphosphorylated tau (p-tau) in three IVIGs, as well as their effects on systemic inflammation induced by lipopolysaccharide (LPS) in Balb/c mice, were analyzed and compared in this study. The results indicated that these IVIGs differed greatly in anti-Aβ42/tau antibody concentration and anti-p-tau ratio, and improved LPS-stimulated peripheral inflammation, liver and kidney injury, and neuroinflammation in Balb/c mice to varying degrees. Combined with our previous results, the efficacy of IVIG against AD may be positively correlated with its level of AD-related antibodies and anti-inflammatory ability. AD-related antibody analysis and functional evaluation of IVIG should be given sufficient attention before clinical trials, as this may greatly affect the therapeutic effect of AD treatment.

Impact of Omicron Variant Infection on Assessment of Spike-Specific Immune Responses Using the EUROIMMUN Quan-T-Cell SARS-CoV-2 Assay and Roche Elecsys Anti-SARS-CoV-2-S

The currently prevailing variants of SARS-CoV-2 are subvariants of the Omicron variant. The aim of this study was to analyze the effect of mutations in the Spike protein of Omicron on the results Quan-T-Cell SARS-CoV-2 assays and Roche Elecsys anti-SARS-CoV-2 anti-S1. Omicron infected subjects ((n = 37), vaccinated (n = 20) and unvaccinated (n = 17)) were recruited approximately 3 weeks after a positive PCR test. The Quan-T-Cell SARS-CoV-2 assays (EUROIMMUN) using Wuhan and the Omicron adapted antigen assay and a serological test (Roche Elecsys anti-SARS-CoV-2 anti-S1) were performed. Using the original Wuhan SARS-CoV-2 IGRA TUBE, in 19 of 21 tested Omicron infected subjects, a positive IFNy response was detected, while 2 non-vaccinated but infected subjects did not respond. The Omicron adapted antigen tube resulted in comparable results. In contrast, the serological assay detected a factor 100-fold lower median Spike-specific RBD antibody concentration in non-vaccinated Omicron infected patients (n = 12) compared to patients from the pre Omicron era (n = 12) at matched time points, and eight individuals remained below the detection threshold for positivity. For vaccinated subjects, the Roche assay detected antibodies in all subjects and showed a 400 times higher median specific antibody concentration compared to non-vaccinated infected subjects in the pre-Omicron era. Our results suggest that Omicron antigen adapted IGRA stimulator tubes did not improve detection of SARS-CoV-2-specific T-cell responses in the Quant-T-Cell-SARS-CoV-2 assay. In non-vaccinated Omicron infected individuals, the Wuhan based Elecsys anti-SARS-CoV-2 anti-S1 serological assay results in many negative results at 3 weeks after diagnosis.

The importance of specific IgE antibodies in the epidemiology of allergic rhinitis and asthma (ECAP survey): part four. The relationship between the concentration of specific IgE antibodies in serum and types of asthma.

Specific immunoglobulins E (sIgE) are important parameters for the estimation of severity of allergic diseases. To determine the relationship between the concentration of specific IgE antibodies in serum and types of asthma. The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, and Alternaria alternata were determined in the serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml or ≥ 0.7 IU/ml) were correlated to clinical diagnosis (types of asthma, skin-prick tests). sIgE antibodies against any allergen were detected in 9.9% (classes 1-6)/7.6% (classes 2-6) of healthy respondents. Comparing sIgE antibodies of respondents with intermittent asthma to sIgE antibodies of respondents with persistent asthma, no statistically significant differences were identified. Relating to allergens of D. pteronyssinus, cat dander, and A. alternata, sIgE antibodies were more frequently detected in respondents with atopic asthma and a negative skin-prick test as compared to healthy respondents with a negative skin-prick test (p < 0.005 to p < 0.001). Relating to allergens of D. pteronyssinus, cat dander, and timothy grass, sIgE antibodies were more frequently detected in respondents with atopic asthma and a weakly positive skin-prick test as compared to healthy respondents with weakly positive skin-prick test (p < 0.05 to p < 0.001). Regarding subjects with a negative or weakly positive skin test, when sIgE antibodies to the same allergen are detected, asthma is much more likely to occur.

The importance of specific IgE antibodies in the epidemiology of allergic rhinitis and asthma (ECAP survey): part five. The relationship between the concentration of specific IgE antibodies in serum and types of rhinitis.

Specific immunoglobulins E (sIgE) are important parameters for the estimation of severity of allergic diseases. To determine the relationship between the concentration of specific IgE antibodies in serum and types of rhinitis. The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, and Alternaria alternata were determined in the serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml or ≥ 0.7 IU/ml) were correlated to clinical diagnosis (types of rhinitis, skin-prick tests). sIgE antibodies are more frequently detected in respondents with intermittent/seasonal allergic rhinitis and a negative skin-prick test as compared to healthy respondents with a negative skin-prick test (p < 0.05 to p < 0.001). Relating to allergens of D. pteronyssinus and cat dander, sIgE antibodies are more frequently detected in respondents with persistent/perennial allergic rhinitis and a negative or weakly positive skin-prick test as compared to healthy respondents with a negative or weakly positive skin-prick test (p < 0.05 to p < 0.001). The occurrence of intermittent/seasonal allergic rhinitis is much more probable in respondents with a negative skin-prick test, when IgE antibodies against the same allergen are detected. And the occurrence of persistent/perennial allergic rhinitis is much more probable in respondents with a negative or weakly positive skin-prick test with allergens of D. pteronyssinus or cat dander, when IgE antibodies against the same allergen are detected.

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Discordant Cellular and Humoral Responses to a 3-Dose COVID-19 mRNA Vaccination Schedule in Patients with Hematologic Malignancies

Introduction Studies in 2-dose COVID-19 vaccinated hematology patients demonstrated reduced humoral immune responses compared to healthy individuals. It has become common practice to offer these patients a 3rd COVID-19 vaccination but data substantiating this are scarce. We quantitatively and qualitatively evaluated humoral as well as cellular responses to a 3-dose vaccination schedule, followed by a 4th vaccination, in a prospectively designed, large and diverse cohort of patients with hematologic malignancies. Methods We prospectively quantified SARS-CoV-2-specific spike glycoprotein 1 immunoglobulin G (S1 IgG) concentration against the first serum standard for COVID-19 (20/136; provided by the National Institute for Biological Standards Control), antibody neutralization capacity of wild-type virus and variants of concern, and SARS-CoV-2-specific CD4+ and CD8+ T cell responses by activation marker expression, cytokine production and peptide-HLA tetramer staining in patients with hematologic malignancies prior to, and 4 weeks after each COVID-19 vaccination. Antibody concentrations were compared to those obtained by age-matched healthy individuals, extracted from a population-based study conducted by the Dutch National Institute for Public Health and the Environment. Previously infected participants, identified as having nucleocapsid (N) IgG >14.3 BAU/ml, were excluded from further analysis. Results In total, 692 patients with a hematologic malignancy were included in the study. In 673 evaluable patients S1 IgG concentrations were significantly lower after the primary 2-dose mRNA-1273 schedule, compared to concentrations in age-matched healthy individuals (Haggenburg et al., Blood Adv 2022). A 3rd mRNA-1273 vaccination led to S1 IgG concentrations comparable to those obtained by age-matched healthy individuals after the primary 2-dose mRNA-1273 schedule (Figure 1). Moreover, a 3rd vaccination significantly improved antibody neutralization capacity against SARS-CoV-2 wild type and variants of concern (not shown). The rise in S1 IgG concentration after the 3rd vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. S1 IgG antibody concentrations remained low in patients receiving, or shortly after, anti-CD20 therapy, CD19-directed chimeric antigen receptor T cell therapy, and in chronic lymphocytic leukemia patients receiving ibrutinib (Figure 1; Haggenburg et al., medRxiv 2022). In most B cell depleted patients, spike-specific CD4+ and, most prominently, CD8+ T cell responses were generated. A dichotomy between humoral and cellular immune responses was also observed in other patient groups: patients with myeloproliferative disease receiving ruxolitinib, multiple myeloma patients receiving immunomodulatory drugs or daratumumab, and patients with chronic graft versus host disease obtained adequate S1 IgG concentrations, but less pronounced SARS-CoV-2-specific, cytokine-producing CD4+ and/or CD8+ T cell responses after each vaccination. This is in contrast to multiple myeloma patients receiving 1st line remission-induction therapy followed by high-dose melphalan and autologous HCT, who generated antibody and CD4+ T cell responses comparable to healthy individuals. In patients with myeloid disease receiving hypomethylating agents S1 IgG antibody and T cell responses were both impaired. A 4th vaccination further improved S1 IgG concentrations in the majority of patients; its effect on cellular immunity is currently being evaluated. Conclusion After a 3-dose mRNA vaccination schedule, the majority of patients with hematologic malignancies obtained adequate antibody concentrations and robust CD4+ T cell responses. However, T and B cell responses were often discordant: the presence of adequate SARS-CoV-2 specific antibody concentrations was not necessarily accompanied by robust T cell immunity and vice versa. The impact of discordant T and B cell responses on vaccine effectiveness requires further investigation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immunogenicity and safety of the booster BNT162b2 vaccine in patients with axial spondyloarthritis treated with biological disease-modifying drugs.

BackgroundVaccination confers relatively short-term protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indicating the need for booster doses. Immunocompromised individuals, including those with immune-mediated inflammatory diseases (IMIDs), may have pronounced immune response waning. Vaccine-boosted humoral and T-cell responses minimize poor coronavirus disease 19 (COVID-19) outcome without increasing adverse events (AE). There is limited evidence of third-dose vaccination in axial spondyloarthritis (AxSpA) patients. We investigated immune-response persistence after primary vaccination and immunogenicity and safety after the BNT162b2 booster vaccination.MethodsThis prospective observational study enrolled an AxSpA cohort treated with interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNFα) inhibitors. Serum SARS-CoV-2-specific and virus-neutralizing antibodies for humoral response and flow cytometric detection of intracellular cytokines following SARS-CoV-2-specific peptide-based stimulation for T-cell immune responses were assessed, and safety was evaluated via a clinical questionnaire.ResultsFifteen male AxSpA patients treated with TNFα (73·3%) or IL-17 (26·7%) inhibitors were enrolled and had humoral response persistence at 6 months: 905·6 ( ± 186·1 SD) and 409·1 ( ± 335·7) U/mL. Specific antibody concentrations further increased after booster vaccination to 989·7 ( ± 12·62) and 1000 U/mL and T-cell responders from 53·3% to 80%, with no differences between AxSpA (including “vaccination only” and “hybrid immunity” subgroups) and healthy control (HC) cohorts. No severe AE occurred; the AE spectrum was comparable to that of the general population.ConclusionImmune-response persistence after primary vaccination and immunogenicity after booster vaccination were unaffected by anti-IL17 or anti-TNFα therapy with similar AE as in the general population.

Association Between Human Immunodeficiency Virus Viremia and Compromised Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Beta Variant.

BackgroundSARS-CoV-2 infection may be associated with worse clinical outcomes in people with HIV (PWH). We report anti-SARS-CoV-2 antibody responses in COVID-19 hospitalized patients in Durban, South Africa during the second SARS-CoV-2 infection wave dominated by the Beta (B.1.351) variant.MethodsThirty-four participants with confirmed SARS-CoV-2 infection were followed up with weekly blood sampling to examine antibody levels and neutralization potency against SARS-CoV-2 variants. Participants included 18 PWH, of whom 11 were HIV viremic.ResultsSARS-CoV-2 specific antibody concentrations were generally lower in viremic PWH relative to virologically suppressed PWH and HIV-negative participants and neutralization of the Beta variant was 4.9-fold lower in viremic PWH. Most HIV-negative participants and ART-suppressed PWH also neutralized the Delta (B.1.617.2) variant, whereas the majority of viremic PWH did not. CD4 counts <500 cells/μL were associated with lower frequencies of IgG and IgA seroconversion. In addition, there was a high correlation between a surrogate virus neutralization test and live virus neutralization against ancestral SARS-CoV-2 virus in both PWH and HIV-negative individuals, but correlation decreased for the Beta variant neutralization in PWH.ConclusionsHIV viremia was associated with reduced Beta variant neutralization. This highlights the importance of HIV suppression in maintaining an effective SARS-CoV-2 neutralization response.

Relationship between the level of specific IgG to neurolep¬tics and the content of autoantibodies to dopamine recep¬tors, dopamine and acetylcholine receptors in patients with schizophrenia

The purpose of the research was to study the levels of autoantibodies (AAB) to dopamine receptors of type 2 (DR2), to dopamine and acetylcholine receptors in the blood of patients with schizophrenia and to identify the relationship between the content of specific antibodies (IgG) to neuroleptics and the amount of autoantibodies.