Immunoglobulin IgG Research Articles

Identification of bacterial protease domains that cleave human IgM

Immunoglobulin-degrading proteases are secreted by pathogenic bacteria to weaken the host immune response, contributing to immune evasion mechanisms during an infection. Proteases specific to IgG and IgA immunoglobulin classes have previously been identified and characterized, and only a single report exists on a porcine specific IgM-degrading enzyme. It is unclear whether human pathogens also produce enzymes that can break down human IgM. Here, we have identified four novel IgM-degrading proteases from different genera of human-infecting bacterial pathogens. All four protease domains cleave human IgM at a conserved and unique site in the constant region of IgM. These human IgM proteases may be a useful biochemical tool for the study of early immune responses and have therapeutic potential in IgM-mediated disease.

Clinical Utility of SARS-CoV-2 Antibody Testing

SARS-CoV-2 antibody assay is a test that checks whether an antibody against the SARS-CoV-2 virus has been formed in the blood after SARS-CoV-2 infection or vaccination. SARS-CoV-2 antibody is detected 1–2 weeks after infection, and antibodies are produced in more than 90% of infected patients. The duration for the formation of antibodies differs by individual and by type of antibody. In the case of IgG, it is at least several months or longer, and the relationship between antibodies and immunity is being studied. As test methods,enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CIA), immunochromatographic assay, and neutralizing antibody assay have been developed and used. The target antibody to be detected differs depending on the type of recombinant antigen and the type of secondary antibody in reagents. Many kinds of commercialized SARS-CoV-2 antibody assays are currently being developed, and the S (spike) protein, N (nucleocapsid) protein, S1 or RBD (receptor binding domain) part of the S protein, and a mixture of these antigens are used as recombinant antigens of reagents. IgG, IgM, IgA, or total immunoglobulin antibodies in patients’ blood that react with these reagent antigens are detected. In this review, the types and performance of SARS-CoV-2 antibody tests and the guidelines for COVID-19 antibody tests published domestically and abroad were investigated.

Raman spectroscopic analysis of human serum samples of convalescing COVID-19 positive patients

Rapid screening, detection and monitoring of viral infection is of critical importance, as exemplified by the rapid spread of SARS-CoV-2, leading to the worldwide pandemic of COVID-19. This is equally the case for the stages of patient convalescence as for the initial stages of infection, to understand the medium and long terms effects, as well as the efficacy of therapeutic interventions. Optical spectroscopic techniques potentially offer an alternative to currently employed techniques of screening for the presence, or the response to infection. In this study, the ability of Raman spectroscopy to distinguish between samples of the serum of convalescent COVID-19 positive patients and COVID-19 negative serum samples, and to further analyse and quantify systemic responses, was explored. The study included serum samples of patients who had been tested for SARS-CoV-2 specific IgG and IgM responses between 25 and 134 days after the infection was identified. Both COVID-19 positive and negative groups included males and females who ranged in age from 21 to 81 years old. No correlation was apparent between the specified SARS-CoV-2 specific IgG and IgM immunoglobulin levels of the positive group, their sex, or age. Raman spectroscopic measurements were performed at 785 nm, in liquid serum, thawed from frozen, and spectra were pre-processed to remove the contribution of water, normalising to the water content. Principal components analysis of the spectral dataset over the range 400–1800 cm-1 provided no clear indication of a difference between normal serum and SARS-CoV-2 positive serum. A selection of 5 of the samples, which were available in sufficient volume, were fractionated by centrifugal filtration, and the 100 kDa, 50 kDa, 30 kDa, and 10 kDa concentrates similarly analysed by Raman spectroscopy. Partial least squares regression analysis revealed a negative correlation between the spectral profile of the 30 kDa fractions and SARS-CoV-2 specific IgG antibody levels, potentially indicating an association with depleted glutathione levels. The study supports a potential role of Raman screening of blood serum for monitoring of SARS-CoV-2 infection, but also in longitudinal studies of disease progression, long term effects, and therapeutic interventions.

Dietary supplementation with American ginseng dietary fiber ameliorates intestinal mucosal barrier injury in immunosuppressed mice

Dietary fiber is an important component of healthy eating patterns. Although American ginseng (Panax quiquefolium L.) is often used to improve body immunity, less attention has been paid to American ginseng dietary fiber (AGDF) in this regard. The aim of this study was to investigate the protective effect of AGDF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and the underlying mechanism. The results showed that AGDF could increase immune organ index and enhance immunity of immunosuppressed mice, such as DTH response, lymphocyte transformation and proliferation and NK effector cell activity. At the same time, AGDF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, and promote the secretion of immunoglobulin IgG. More importantly, AGDF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1β in serum and intestine of immunosuppressed mice, promote the secretion of cytokines and regulate the homeostasis balance between Th1/Th2 cytokines. It also upregulated the expression of tight junction proteins occludin, claudin-1 and ZO-1, and alleviated the degree of CTX-induced damage to the intestinal mucosal barrier. Meanwhile, AGDF could reduce intestinal epithelial cell apoptosis by activating TLR4/NF-κB signaling pathway, improving the phosphorylation of JNK and p38 signaling molecules, which may be the potential mechanism by which AGDF ameliorates intestinal mucosal injury in immunosuppressed mice. Therefore, AGDF may be used as a dietary supplement to prevent and treat intestinal mucosal barrier injury caused by CTX.

Detection and characterization Salmonella enterica from broiler chicken(Rose308) in Thi-Qar province and its relationship to broiler immunity and body weight

This study was conducted to isolate Salmonella bacteria from broiler (ROSS 308). A total of 184 stool samples were collected from chickens, showed symptoms of infection with salmonella bacteria from two different fields in Thi-Qar Governorate in Al-Islah district and Al-Fadeliyah district. Thirty isolates (16.2%) were diagnosed with Salmonella infection by biochemical and API 20 E tests. The pathological infection was confirmed in chickens by analyzing the level of antibodies in the blood of chickens, there was an increase in the level of immunoglobulin IgG and IgM, confirmed the existence of the disease and the stage of infection between a new infection and the acquisition of immunity, as a result of the previous injury and injuries close to recovery. The birds that suffer from a lack of weight differed in the stage of infection, this indicates that infection at any stage has a significant impact on the weights of birds infected with salmonella bacteria.

Selektif IgE Eksikliği ve Otoimmun Hastalık İlişkisi

Abstract
 Introduction and Aim: Selective IgE deficiency (SIgED) is currently defined as a significant decrease in serum levels of IgE (≤2 kIU/L) in a patient whose other immunoglobulin levels are normal. The clinical spectrum of SIgED is unknown still. This study aimed to determine the relationship between SIgED and autoimmune diseases in an allergy and immunology clinic of a university hospital.
 Methods: A retrospective study of the data obtained from medical records of 40 patients, 27 were female (67.5%), and the mean age was 39 years (range 20–69 years) and IgE levels of ≤2.0 kIU/L with normal immunoglobulin (Ig) IgG, IgA, and IgM levels.
 Results: A total of 40 patients , 27 females (67.5 %) and 13 males (32.5%), were included in the study. The mean age of the patients was 39 ±13.06 years (range 20–69). In the present study, 35% of patients had an autoimmune disease (N:14), however 65% of patients did not have any autoimmune disease (N:26). Hashimoto’s thyroiditis being the most frequent (N:6) in 15% which is followed by systemic lupus erythematosus (SLE) (N:3) in 7.5%, celiac disease (N: 2) in 5%, chronic spontaneous urticaria (CSU) (N:1) in 2.5%, vitiligo (N:1) in 2.5%, type 1 diabetes mellitus (DM) (N:1) in 2.5%. 
 Conclusion: SIgED, should be defined clearly with cut-off values of IgE. Physicians should show more attention to the low IgE values and investigate patients about autoimmune diseases which can be seen together with SIgED. More studies should be conducted to investigate associated diseases with SIgED.

Comparison of four commercial immunomagnetic separation kits for the detection of Cryptosporidium.

Cryptosporidium spp. are protozoan parasites of significant health importance found in environmental waters globally. Four commercially available Cryptosporidium-specific immunomagnetic separation (IMS) kits used in various water sample matrices were analysed and compared. Beads were characterised by flow cytometry and tested for the recovery efficiencies for oocysts spiked into different matrices: river water sediment, clay sample, and filter backwash sample. Results showed that Dynabeads™ Cryptosporidium and Waterborne Crypto-Grab™ kits contained immunoglobulin IgM antibody-coated beads. In contrast, the BioPoint CryptoBead and the TCS Isolate kits contained immunoglobulin IgG antibody-coated beads. BioPoint CryptoBead was significantly coated with more antibodies and were able to capture oocysts more rapidly compared to the other beads. Recovery efficiencies of Dynabeads™, TCS Isolate® beads, and BioPoint CryptoBead ranged from 55 to 93% when tested against different sample matrices, with BioPoint CryptoBead resulting in the highest at 93% in reagent-grade water and Dynabeads™ at 55%, the lowest against clay samples. The Waterborne beads did not perform well on any samples, with recovery efficiencies ranging from 0 to 8%. Fluorescence microscopy analyses showed that both the IMS method and the sample matrix processed affect the quality of the membranes, with the cleanest samples for microscopy examination observed from BioPoint CryptoBead.

B-181 Multi-centre Analytical Performance Evaluation of the EXENTâ Solution for Identification and Quantitation of Monoclonal Immunoglobulins

Abstract Background Current routine methodologies for monoclonal immunoglobulin measurements may not be sufficiently sensitive to reflect the depth of response seen in patients since the introduction of novel therapies; mass spectrometry may offer a valuable, sensitive alternative approach. Here we describe the preliminary analytical performance characteristics of the EXENT® solution (in development by The Binding Site, part of Thermo Fisher scientific) that combines specific immunoprecipitation steps and mass spectrometry for the identification and quantification of IgG, IgA and IgM intact monoclonal immunoglobulins. Each intact monoclonal immunoglobulin clone can be tracked using its unique m/z value. Methods The Lower Limit of Measuring Interval (LLMI) was established for each immunoglobulin type following EP17-A2:2012. Linearity studies were performed according to CLSI EP06-A2:2020 using high and low pools of IgG, IgA, and IgM monoclonal samples and with additional linearity testing below 1 g/L for each specificity to more effectively demonstrate low-end linearity. Within run, between run, between analyzer, between lot and total precision for M protein concentrations and for molecular mass (m/z) of the monoclonal peaks were assessed according to CLSI EP5-A3-2014. Interference was tested following ED3:2018 using 20 potential interferents against 7 samples including high and low IgG, IgA and IgM monoclonal samples. Results The initial indication of the EXENT solution performance, in development, are set out below. Results suggest an analytical sensitivity of the assays around 15 mg/L at the LLMI for all specificities. Linearity over a range of 0.014–88.9 g/L for IgG, 0.011–68.4 g/L for IgA, and 0.11–74.2 g/L for IgM. Coefficients of variation (CVs) for M protein concentrations in precision studies were <15% for all specificities and samples. Mass/charge values were within ±1.1 to ±1.5 m/z in total precision studies, and within ±2.7 to ±3.9 m/z in between lot precision studies, respectively, for M proteins with an m/z value ranging from 11 360.6 to 11 698.5 m/z. No significant interference effects were observed when testing the 20 interferents including intralipid (20 g/L), triglyceride (15 g/L), bilirubin (400 mg/L), rheumatoid factor (200 IU/mL) and haemoglobin (10 g/L). Conclusion The new EXENT solution demonstrates the potential for a wide measuring interval and the ability to detect M proteins with very low concentration. Also, it could provide stable and reproducible performance for the detection and typing of monoclonal immunoglobulins.

Impact of blood-brain barrier disruption on clinical features and treatment response in patients with newly diagnosed autoimmune encephalitis

AimsBlood-brain barrier (BBB) breakdown is an essential mechanism in inflammatory diseases of the central nervous system. However, the association between BBB integrity and autoimmune encephalitis (AE) has not been investigated. Our study aimed to analyze this relationship in patients with AE between BBB integrity with clinical manifestations and therapeutic responses. MethodsOur study enrolled 147 patients with AE who were newly diagnosed at the First Affiliated Hospital of Zhengzhou University between August 2015 and December 2021. Patients were classified into normal or damaged BBB groups based on cerebrospinal fluid (CSF) albumin/serum albumin (QAlb). To evaluate the severity of the illness, we used the modified Rankin Scale (mRS) and the Clinical Assessment Scale for Autoimmune Encephalitis (CASE). ResultsWe found a higher proportion of males, higher CSF protein, immunoglobulin IgG, and 24-h intrathecal IgG synthesis rate in the damaged BBB group. The improvement rate was lower in the damaged BBB group, but we found that double- or triple-combination immunotherapy had better clinical outcomes than single immunotherapy. In addition, there was a positive correlation between the CASE score and mRS score, and a positive correlation between the CASE score or mRS score and QAlb on admission. ConclusionsBBB integrity is closely related to the clinical features and treatment responses of newly diagnosed AE. Patients with AE and a damaged BBB may benefit from combination immunotherapy.

Effect of different levels of Moringa oleifera seed powder to the diet on some immunological and histological parameters of common carp fish Cyprinus carpio L.

75 common carp fish with an average weight of 65.08±0.42 g were used. The fish were fed on experimental diets, which were divided into five equal treatments in terms of protein percentages, different in the proportions of adding Moringa seed powder, was 0, 0.5, 1, 1.5 and 2%, respectively; the fish were fed on the experimental diets at 5% of the live weight, divided into 4 meals a day. The liver histological examinations in T2 and T3-treated fish showed a significant improvement in the histological characteristics of hepatocytes and the contents of the liver tissue parenchyma. At the same time, it was observed that the liver tissue was slightly affected in the fish of the fourth and fifth treatments without affecting the health status of the fish. Histological examinations also showed the improvement and superiority of T2, T3, T4 and T5 treatment fish compared to control treatment fish on histological parameters of small intestine and gill tissue. This indicates that adding Moringa seed powder to fish diets at low rates stimulated the immune system and raised the concentration of IgM and IgG immunoglobulins to improve the fish's tissue health status. Keywords: Moringa oleifera, immunological, histological, common carp fish Cyprinus carpio L.

In-Ovo injection of melittin into Alexandria chicken eggs: a way for early immune acceleration

This study intended to assess the properties of in-ovo administration of Melittin (MLT) on hatchability, chick yield, hematology, immunological indices and relative organs weight of Alexandria chickens at hatch. A total of 600 eggs with an average weight of (45.12 g), were gathered and split into five groups: a non-injected group or negative control (NC), a saline injection group or positive control (PC), and three concentrations of MLT (5, 10 and 15 µg of MLT per egg, respectively). On day 18 of incubation, eggs from the injection groups were injected into the amniotic fluid from the large end with the in-ovo injection solutions (0.2 ml per egg). Results indicated that 10 µg MLT/egg positively affected the weight and yield of chicks. In addition, our findings indicated that the in-ovo administration with 10 or 15 µg MLT/egg was superior in most of the immunological indicators (spleen and bursa relative weights, immunoglobulins IgG and IgM, T cells and B cells). In conclusion, in order to improve the immune efficiency (early immune acceleration) of Alexandria chicks, which may contribute to offering a significant boost to their future performance, this study suggests injecting eggs with 5 or 10 µg MLT/egg.

Seroprevalence and Identification of Brucella melitensis Based on a Glycosyltransferase Gene among Ruminants in Rafha, Saudi Arabia

Brucellosis is a zoonotic disease with veterinary, public health, and economic implications. The study aimed to estimate the seroprevalence of Brucella spp. among ruminants in Rafha, Saudi Arabia during January to October 2022 and to identify camel strains based on a glycosyltransferase gene sequence. Sera (n=1012) were collected from non-vaccinated sheep, goats, camels and cattle of different sex, age and breed randomly from the abattoirs to investigate the circulating brucella antibodies using RBPT. One hundred and eighteen sera (9.7%) were reactive for Brucella spp. IgG immunoglobulins, with higher percentages detected in sheep (11.4%), females (13.3%), adults (10.7%), and naieme breed (13.9%). Significant correlation between Brucella spp. antibodies and animal species (0.095), age (0.077) was found, while strong correlation between antibodies and sex was observed. Glycosyltransferase gene was amplified and sequenced from camel reactive sera (n=6). Camel strains displayed multiple nucleotide substitutions and deletions, nucleotide identity among local strains is 96.2-100%. Phylogenetic analysis showed that Brucella spp. strains clustered in two groups, Rafha strains clustered in one group together with other strains. Further investigation is needed to determine the prevalence of the bacteria among farm animals and to identify the strains involved to improve the preventive measures and strategies adopted for control.

The enhanced direct antiglobulin test in current practice has a limited impact on management of adult patients

IntroductionThe direct antiglobulin test (DAT) identifies immunoglobulin IgG and/or complement onthe red blood cell surface, allowing discrimination between immune and non-immunehemolysis. When the DAT is negative but there is clinical suspicion for immunehemolysis, an enhanced DAT can be sent to an immunohematology referencelaboratory (IRL). MethodologyThis retrospective study assessed the volume of enhanced DATs at a large tertiarycare center and evaluated their impact on patient care. Enhanced DATs were sent on21 adult patients (January 2019 - January 2021) at the University of Pittsburgh MedicalCenter and Allegheny Health Network. Laboratory and clinical data were collected andanalyzed. ResultsFour out of 21 patients had positive tests (DAT and other serologic tests) at the localIRL. Enhanced DAT testing yielded positive results in an additional 5 patients butnegative or invalid results for 2 patients. High-dose steroid therapy was started in 12patients prior to receipt of enhanced DAT results. Enhanced DAT testing was sent amedian of 5 days after initiation of steroid therapy. For the patients trialed on steroids,the enhanced DAT results impacted medical decision-making in only 3 patients, and inonly one of those patients was the enhanced DAT positive despite a negative DAT at alocal IRL. In the non-steroid treated patients, enhanced DAT results did not contributeto clinical decision-making. ConclusionEnhanced DATs generally did not impact medical decision-making in adults withhemolytic anemia.

Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients.

Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post-AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries. We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient-specific, disease-specific, and transplant-specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen-related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100. Ninety-five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33-68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4-144). Eighty-nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile-associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9-14) and 12 days (range 9-23), respectively. The median duration of hospital stay was 16 days (range 9-29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant-related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10vs. day +11) and platelet engraftment (day +11vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression-free survival of the study population at 5 years were 72.7% and 64.8%, respectively. This study shows that the incidence of infections and TRM are higher in MM patients from lower-middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis.

Bacteriocin-Producing Lactiplantibacillus plantarum YRL45 Enhances Intestinal Immunity and Regulates Gut Microbiota in Mice.

Bacteriocins production is one of important beneficial characteristics of probiotics, which has antibacterial property against intestinal pathogens and is helpful for regulating intestinal flora. To investigate the impact of bacteriocin-producing probiotics on gut microecology, bacteriocin-producing Lactiplantibacillus plantarum YRL45 was orally administered to mice. The results revealed that it promoted the release of cytokines and improved the phagocytic activity of peritoneal macrophages to activate the immune regulation system. L. plantarum YRL45 was conducive to maintaining the morphology of colon tissue without inflammation and increasing the ratio of villus height to crypt depth in the ileum. The gene expression levels of Muc2, ZO-1 and JAM-1 were significantly up-regulated in the ileum and colon, and the gene expression of Cramp presented an upward trend with L. plantarum YRL45 intervention. Moreover, L. plantarum YRL45 remarkably enhanced the levels of immunoglobulins sIgA, IgA and IgG in the intestine of mice. The 16S rRNA gene analysis suggested that L. plantarum YRL45 administration up-regulated the relative abundance of the beneficial bacteria Muribaculaceae and Akkermansia, down-regulated the abundance of the pathogenic bacteria Lachnoclostridium, and promoted the production of acetic acid, propionic acid and total short-chain fatty acids (SCFAs) in mice feces. Our findings indicated that L. plantarum YRL45 had the potential to be developed as a novel probiotic to regulate the intestinal barrier by altering gut microbiota to enhance intestinal immunity and ameliorate intestinal flora balance.

New high-throughput screening method for Chinese hamster ovary cell lines expressing low reduced monoclonal antibody levels: application of a system controlling the gas phase over cell lysates in miniature bioreactors and facilitating multiple sample setup.

Interchain disulfide bonds in monoclonal antibodies may be reduced during large-scale mAb production using Chinese hamster ovary (CHO) cells. This reaction lowers the mAb product yield and purity; however, it may be prevented by screening cell lines that are unsusceptible to reduction and using them in mAb production. Antibody reduction susceptibility may be cell line-dependent. To the best of our knowledge, however, an efficient method of screening reduction-unsusceptible CHO cell lines has not been previously reported. Here, we report a novel screening method that can simultaneously detect and identify mAb reduction susceptibility in lysates containing ≤ 48 CHO cell lines. This evaluation system was equally effective and generated similar results at all culture scales, including 250 mL, 3L, and 1000L. Furthermore, we discovered that reduction-susceptible cell lines contained higher total intracellular nicotinamide adenine dinucleotide phosphate (NADPH) and NADP+ concentrations than reduction-unsusceptible cell lines, regardless of whether they expressed immunoglobulin (Ig)G4 or IgG1. NADPH or NADP+ supplementation in the lysate of reduction-unsusceptible cells resulted in mAb reduction. Application of the innovative CHO cell line screening approach could mitigate or prevent reductions in large-scale mAb generation from CHO cells.

THE ROLE OF COLOSTURAL INDICATORS IN PREVENTION CORONAVIRUS AND ROTAVIRAL DIARRHEA IN CALVES

One of the main conditions for increasing the productivity of animal husbandry is the protection of newborn calves from early death. The leading place among these diseases belongs to infectious diseases with the diarrhea syndrome in newborns. Gastrointestinal diseases of calves, as usually, are polyetiological in nature and caused by various infectious agents: viruses, bacteria, chlamydia, mycoplasmas, fungi, protozoa and others. In the presented study, indicators of the quality of colostrum and vaccination of newborn calves were measured, and such indicators in animals as proteins, fats, lactose, IgG immunoglobulin levels were analyzed. Experiments were carried out on 50 animals. The results obtained confirmed that high-quality colostrum increases the resistance of calves to diseases.

Effectiveness and Safety of Eptinezumab in Episodic and Chronic Migraine Headache in the UAE: A Retrospective Study.

Eptinezumab is a humanized IgG1 immunoglobulin monoclonal antibody administered intravenously as a preventative migraine treatment. Previously conducted randomized, double-blind, placebo-controlled trials exhibited significant reductions in monthly migraine frequency among adults experiencing episodic and chronic migraine. The present study seeks to expand upon the current findings and to evaluate eptinezumab's efficacy as a preventative treatment for chronic and episodic migraine patients in the United Arab Emirates. This study is intended to represent the first real-world evidence and will hopefully serve as a valuable complement to the existing literature on the subject. This was a retrospective exploratory study. The participants included within the study were adult (≥18years) patients diagnosed with either episodic or chronic migraine. Patients were categorized according to their history of previous preventative treatment failure. For the final assessment of treatment efficacy, we included only patients with a minimum of 6months of clinical follow-up data. Patients were assessed at baseline for their monthly migraine frequency and assessed again at months 3 and 6. The primary objective was to evaluate the efficacy of eptinezumab in reducing migraine frequency among chronic and episodic migraine patients. A total of 100 participants were identified, of whom 53 completed the study protocol at month 6. Of the total, 40 (75.47%) were female, 46 (86.79%) were Emirati locals, and 16 (30.19%) were pharmaceutically naïve, having never tried any prior preventative therapy. Additionally, 25 (47.17%) patients met the criteria for chronic migraine (CM), whereas the remaining 28 (52.83%) were diagnosed with episodic migraine (EM). The baseline monthly migraine frequency (MMD) was 12.23 (4.97) days across all participants, 15.56 (3.97) for CM patients, and 9.25 (3.76) for EM patients; by month 6, these frequencies reduced to 3.66 (4.21), 4.76 (5.32), and 2.68 (2.61), respectively. Overall, 58.49% of those enrolled experienced>75% reduction in MMD frequency by month 6. Patients enrolled in this trial experienced clinically significant reductions in MMD by month 6. Eptinezumab was well tolerated and with one AE of significance that led to discontinuation from the study.

A fully human monoclonal antibody possesses antibody-dependent cellular cytotoxicity (ADCC) activity against the H1 subtype of influenza A virus by targeting a conserved epitope at the HA1 protomer interface.

The DiversitabTM system produces target specific high titer fully human polyclonal IgG immunoglobulins from transchromosomic (Tc) bovines shown to be safe and effective against multiple virulent pathogens in animal studies and Phase 1, 2 and 3 human clinical trials. We describe the functional properties of a human monoclonal antibody (mAb), 38C2, identified from this platform, which recognizes recombinant H1 hemagglutinins (HAs) and induces appreciable antibody-dependent cellular cytotoxicity (ADCC) activity in vitro. Interestingly, 38C2 monoclonal antibody demonstrated no detectable neutralizing activity against H1N1 virus in both hemagglutination inhibition and virus neutralization assays. Nevertheless, this human monoclonal antibody induced appreciable ADCC against cells infected with multiple H1N1 strains. The HA-binding activity of 38C2 was also demonstrated in flow cytometry using Madin-Darby canine kidney cells infected with multiple influenza A H1N1 viruses. Through further investigation with the enzyme-linked immunosorbent assay involving the HA peptide array and 3-dimensional structural modeling, we demonstrated that 38C2 appears to target a conserved epitope located at the HA1 protomer interface of H1N1 influenza viruses. A novel mode of HA-binding and in vitro ADCCactivity pave the way for further evaluation of 38C2 as a potential therapeutic agent to treat influenza virus infections in humans.

Positively Charged-Amylose-Entangled Au-Nanoparticles Acting as Protein Carriers and Potential Adjuvants to SARS-CoV-2 Subunit Vaccines

The COVID-19 pandemic continues to spread worldwide. To protect and control the spread of SARS-CoV-2, varieties of subunit vaccines based on spike (S) proteins have been approved for human applications. Here, we report a new subunit vaccine design strategy that functions as both an antigen carrier and an adjuvant in immunization to elicit high-level immune responses. The complex of 2-hydroxypropyl-trimethylammonium chloride chitosan and amylose entangles Au nanoparticles (HTCC/amylose/AuNPs) forming 40 nm nanocarriers with a positive charge. The obtained positively charged nanoparticles reveal many merits, including the larger S protein loading capacity in PBS buffer, higher cellular uptake ability, and lower cell cytotoxicity, supporting their potential as safe vaccine nanocarriers. Two functionalized nanoparticle subunit vaccines are prepared via loading full-length S proteins derived from SARS-CoV-2 variants. In mice, both prepared vaccines elicit high specific IgG antibodies, neutralize antibodies, and immunoglobulin IgG1 and IgG2a. The prepared vaccines also elicit robust T- and B-cell immune responses and increase CD19+ B cells, CD11C+ dendritic cells, and CD11B+ macrophages at the alveoli and bronchi of the immunized mice. Furthermore, the results of skin safety tests and histological observation of organs indicated in vivo safety of HTCC/amylose/AuNP-based vaccines. Summarily, our prepared HTCC/amylose/AuNP have significant potential as general vaccine carriers for the delivery of different antigens with potent immune stimulation.