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The paper describes the synthesis of an aminopropyl glycoside of hexasaccharide structurally related to the branched fragment of Candida utilis glucomannan, consisting of tetra-α-(1→2)-d-mannoside, the non-reducing end of which is glycosylated with α-glucopyranose and α-mannopyranose residues attached through the (1→2) and (1→3) linkages, respectively. The target structure was assembled by block synthesis with controlled α-stereoselectivity of formation of each glycosidic bond. The resulting hexasaccharide was further converted to a biotinylated conjugate, which, together with previously synthesized similar oligosaccharides, will be used to study the antigenic properties of mannans of Candida fungi. [ABSTRACT FROM AUTHOR]

This paper analyzes the literature data on the role of cytokines in the pathogenesis of malignant neoplasms. Cytokines are biologically active, hormone-like proteins that regulate a wide range of processes occurring in the body. Cytokines determine the type and duration of the immune response, stimulation or suppression of cell growth, and their differentiation and functional activity. The complex of cytokines produced in the tumor microenvironment play an important role in the pathogenesis of malignant neoplasms. The spectra of biological activities of cytokines in most cases overlap. The same process in a cell can be stimulated by more than one cytokine, creating a favorable environment for the initiation and progression of cancer. The immune system can recognize transformed cells. Various cytokines correspond to specific pathways activated by receptors on the cell surface, which, in turn, induce intracellular signaling cascades that affect targeted cellular functions. Cytokine genes are mutually associated with oncogenes. Cytokines that are released in response to infection or inflammation or in the course of an immune response to an antigen can suppress tumor development. In turn, cytokines that attenuate apoptosis and promote invasion and metastasis promote tumor growth. Cytokines are involved in the initiation, development, and metastasis of malignant neoplasms through various mechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: The detection of animal viruses remains a formidable scientific challenge, while concurrently presenting a profoundly consequential practical concern of considerable magnitude, necessitating the development of rapid, sensitive, specific, on-site, cost-effective, and user-friendly diagnostic assays. In response to this demand, electrochemical biosensors have garnered significant attention from researchers. In our review, we comprehensively assess the recent research progress pertaining to electrochemical biosensors for animal viral detection, with a particular focus on the application of screen-printed electrodes. Animal viruses are a significant threat to animal health and are easily spread across the globe with the rise of globalization. The limitations in diagnosing and treating animal virus infections have made the transmission of diseases and animal deaths unpredictable. Therefore, early diagnosis of animal virus infections is crucial to prevent the spread of diseases and reduce economic losses. To address the need for rapid diagnosis, electrochemical sensors have emerged as promising tools. Electrochemical methods present numerous benefits, including heightened sensitivity and selectivity, affordability, ease of use, portability, and rapid analysis, making them suitable for real-time virus detection. This paper focuses on the construction of electrochemical biosensors, as well as promising biosensor models, and expounds its advantages in virus detection, which is a promising research direction. [ABSTRACT FROM AUTHOR]

Introduction: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Methods: Serum and BALF from healthy horses (HE, n = 18) and horses with mildmoderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidylpeptidase 5, class II aldolase/adducin domain protein, glucoamylase, betahexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by beadbased assays. Results: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Discussion: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis. [ABSTRACT FROM AUTHOR]

Tick and tick-borne disease control have been a serious research focus for many decades. In a global climate of increasing acaricide resistance, host immunity against tick infestation has become a much-needed complementary strategy to common chemical control. From the earliest acquired resistance studies in small animal models to proof of concept in large production animals, it was the isolation, characterization, and final recombinant protein production of the midgut antigen Bm86 from the Australian cattle tick strain of Rhipicephalus (Boophilus) microplus (later reinstated as R. (B.) australis) that established tick subunit vaccines as a viable alternative in tick and tick-borne disease control. In the past 37 years, this antigen has spawned numerous tick subunit vaccines (either Bm86-based or novel), and though we are still describing its molecular structure and function, this antigen remains the gold standard for all tick vaccines. In this paper, advances in tick vaccine development over the past three decades are discussed alongside the development of biotechnology, where existing gaps and future directives in the field are highlighted. [ABSTRACT FROM AUTHOR]

CD39 is the rate-limiting enzyme for the molecular signal cascade leading to the generation of ADP and adenosine monophosphate (AMP). In conjunction with CD73, CD39 converts adenosine triphosphate (ATP) to ADP and AMP, which leads to the accumulation of immunosuppressive adenosine in the tumor microenvironment. This review focuses on the role of CD39 and CD73 in immune response and malignant progression, including the expression of CD39 within the tumor microenvironment and its relationship to immune effector cells, and its role in antigen presentation. The role of CD39- and CD73-targeting therapeutics and cancer-directed clinical trials investigating CD39 modulation are also explored. Executive summary Enzyme structure CD39 is an integral membrane protein that dephosphorylates adenosine triphosphate (ATP) to adenosine monophosphate (AMP) and CD73 further dephosphorylates AMP to adenosine (ADO). These enzymes are expressed on different cell types within the tumor microenvironment. Tumor microenvironment Tumor activity and host immune response hinge on the delicate balance between ATP and ADO accumulation within the tumor microenvironment and include the activation of receptors such as A2A and P2X7. CD39 as a biomarker CD39 expression has been identified as a clinically significant positive predictor of ovarian cancer response to immunotherapy. CD39 & CD73 inhibitor trials Anti-CD39 and anti-CD73 monoclonal antibodies are currently being investigated in clinical trials as monotherapies and in combination, with many underway. Oleclumab, an anti-CD73 monoclonal antibody, has recently been shown to be effective with a tolerable safety profile in treating non-small-cell lung cancer with EGFR mutation and will be moving to phase II (NCT03381274). [ABSTRACT FROM AUTHOR]

Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. Cryptococcal antigen (CrAg) testing from serum and cerebrospinal fluid (CSF) has been regarded as a gold standard for early diagnosis. This study aimed to develop and validate a rapid and sensitive sandwich chemiluminescent magnetic microparticle immunoassay (CMIA) for quantitative detection of CrAg in sera. CMIA is based on magnetic beads modified with capture antibodies and biotinylated antibodies and Streptavidin-polyHRP, where biotinylated antibodies functioned as the recognition element and Streptavidin-polyHRP as the signal component. Assay parameters were first optimized, and then assay performances were evaluated. Under optimized conditions, the total runtime of the CMIA was 22 min. The assay had a wide linear range (2 –10,000 ng/mL) and high analytical sensitivity (0.24 ng/mL), together with acceptable reproducibility, accuracy, and stability. Besides, it exhibited no cross-reactivity with other pathogens. Importantly, the assay showed 92.91% (95% CI, 80.97–93.02%) overall qualitative agreement with a commercial ELISA kit in a retrospective cohort of 55 cases with confirmed cryptococcal infection, and 72 controls without evidence of invasive fungal disease (IFD). These results demonstrated that the present study paved a novel strategy for reliable quantitative detection of CrAg in sera. [ABSTRACT FROM AUTHOR]

Objective: Although human blood consists of the same basic parts (red blood cells, white blood cells, platelets, and plasma), there are a large variety of blood groups and types, each with its own different characteristics. The aim of this study to search the correlation between different types of blood groups and increase risk factor for type 2 diabetic mellitus disease. Methods: Blood is made up of several components, and all of these can be utilized to management a lot of different illness. What makes a blood type different is the combination of protein molecules called antigens and antibodies. A person's blood type is also considered to be inherited from the parents' genes. Diabetic mellitus type 2 is related with a type of a chronic illness that effect the trend of the cells in the body for receive glucose or the amount of insulin which synthesize in the pancreas, thus leads to an abnormal decrease or increase in the scale of glucose in the blood. Results: Blood type O had a low risk of diabetes for women with type A, and same for women with type A. Group AB, and low persent of type B, compared with blood group O, have poor chances of developing diabetes. Conclusions: The effect of blood types should be investigated in future clinical and epidemiological studies on diabetes, also there is a need for more research on the pathophysiological mechanism to explain why diabetes has people of group O have a low risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic has resulted in an unprecedented level of worldwide testing for epidemiologic and diagnostic purposes, and due to the extreme need for tests, the gold-standard Reverse Transcription Polymerase Chain Reaction (RT-PCR) testing capacity has been unable to meet the overall worldwide testing demand. Consequently, although the current literature has shown the sensitivity of rapid antigen tests (RATs) to be inferior to RT-PCR, RATs have been implemented on a large scale without solid data on performance. Objective: This study will compare analytical and clinical sensitivities and specificities of 50 lateral flow-- or laboratory-based RATs and 3 strand invasion--based amplification (SIBA)-RT-PCR tests from 30 manufacturers to RT-PCR testing of samples obtained from the deep oropharynx. In addition, the study will compare sensitivities and specificities of the included RATs as well as RT-PCR on clinical samples obtained from the deep oropharynx, the anterior nasal cavity, saliva, the deep nasopharynx, and expired air to RT-PCR on deep oropharyngeal samples. Methods: In the prospective part of the study, 200 individuals found SARS-CoV-2 positive and 200 individuals found SARS-CoV-2 negative by routine RT-PCR testing will be retested with each RAT, applying RT-PCR as the reference method. In the retrospective part of the study, 304 deep oropharyngeal cavity swabs divided into 4 groups based on RT-PCR quantification cycle (Cq) levels will be tested with each RAT. Results: The results will be reported in several papers with different aims. The first paper will report retrospective (analytical sensitivity, overall and stratified into different Cq range groups) and prospective (clinical sensitivity) data for RATs, with RT-PCR as the reference method. The second paper will report results for RAT based on anatomical sampling location. The third paper will compare different anatomical sampling locations by RT-PCR testing. The fourth paper will focus on RATs that rely on central laboratory testing. Tests from 4 different manufacturers will be compared for analytical performance data on retrospective deep oropharyngeal swab samples. The fifth paper will report the results of 4 RATs applied both as professional use and as self-tests. The last paper will report the results from 2 breath tests in the study. A comparison of sensitivity and specificity between RATs will be conducted using the McNemar test for paired samples and the chi-squared test for unpaired samples. Comparison of the positive predictive value (PPV) and negative predictive value (NPV) between RATs will be performed by the bootstrap test, and 95% CIs for sensitivity, specificity, PPV, and NPV will be calculated as bootstrap CIs. Conclusions: The study will compare the sensitivities of a large number of RATs for SARS-CoV-2 to with those of RT-PCR and will address whether lateral flow--based RATs differ significantly from laboratory-based RATs. The anatomical test locations for both RATs and RT-PCR will also be compared. [ABSTRACT FROM AUTHOR]

The simulation of immune response is a challenging task because quantitative data are scarce. Quantitative theoretical models either focus on specific cell–cell interactions or have to make assumptions about parameters. The broad variation of, e.g., the dimensions and abundance between lymph nodes as well as between individual patients hampers conclusive quantitative modeling. No theoretical model has been established representing a consensus on the set of major cellular processes involved in the immune response. In this paper, we apply the Petri net formalism to construct a semi-quantitative mathematical model of the lymph nodes. The model covers the major cellular processes of immune response and fulfills the formal requirements of Petri net models. The intention is to develop a model taking into account the viewpoints of experienced pathologists and computer scientists in the field of systems biology. In order to verify formal requirements, we discuss invariant properties and apply the asynchronous firing rule of a place/transition net. Twenty-five transition invariants cover the model, and each is assigned to a functional mode of the immune response. In simulations, the Petri net model describes the dynamic modes of the immune response, its adaption to antigens, and its loss of memory. [ABSTRACT FROM AUTHOR]

The paper aimed to present the Physiological Tolerance Test of Combination Treatment of Antigen-G and Curcumin Extract on VEGF Levels, Mortality Rate of BALB/c. This research consists of several stages. The TMd-G antigen (ITMd) was isolated from the thoracic segments of Musca domestica larvae 4th instar stage and the thoracic segments of the adult cycle stage, 5 days old. The larvae were obtained from the rearing process using defined media. Curcumine extract (EK) was obtained from Curcuma xanthorrhiza rhizomes through the process of broyage, mixing, precipitation, lyophilization and collection of dry EK. The VEGF serum molecules were significant higher (P<0.05) in Ek20Ag3 to Ek20Ag9 then in other combination treatment. The zero-mortality rate obtained in using AgLMd. [ABSTRACT FROM AUTHOR]

Background: CA 19-9 is a commonly assessed tumor marker, considered characteristic of pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers; however, the positive predictive value of CA 19.9 is too low, and the usage of CA 19.9 as a screening tool in the healthy population remains controversial. Methods: The presented case illustrates a reversed diagnosis of highly elevated serum CA 19-9 levels in a 54-year-old female complaining of pain in the epigastric region, shortly after COVID-19 vaccination. Laboratory tests showed a significantly elevated level of the CA 19-9 marker (>12,000 U/mL, reference value: <37 U/mL) with normal pancreatic enzyme activity. The patient underwent imaging examination, which showed no abnormalities, except for increased pancreatic dimension and areas of fluid signal in the pancreas in magnetic resonance imaging (MRI), which may correspond to autoimmune pancreatitis (AIP). The patient remains asymptomatic with a recommendation for a follow-up MRI in 12 months. Results: A literature review conducted revealed multi-causal CA 19-9 increases above 1000 U/mL, including non-cancerous diseases of the lung, pancreas, liver, ovary, kidney, and others. The median concentration of CA 19-9 regardless of the cause of disease was 2810 U/mL (IQR ± 6895). The median CA 19-9 values in men and women were 3500 (IQR ± 10,050) and 2455 (IQR ± 3927), respectively, and differ significantly between the compared groups (p < 0.05). There was no difference between CA 19-9 values and the categorized cause of the increase. Conclusions: Conducting differential diagnosis, it should not be forgotten that most international guidelines recommend the use of CA 19-9 only in conjunction with pathology of pancreas in radiological imaging; however, even such a combination can point the diagnostic pathway in the wrong direction. A highly elevated CA 19-9 level, typically associated with PDAC, may be the result of benign disease including AIP related to COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

In a post-growth multicellular organism, the phenomenon in which a small number of rare cells can be the starting point for inducing a dramatic change in the entire system is considered a "biological singularity." The immune response and cancer can be regarded as singularity phenomena in mammals, but their nature is fundamentally different. The immune response is considered a "programmed" singularity, whereas cancer is an "unprogrammed" singularity. These two systems perpetually engage in a cycle of attack and defense within the organism. The outcome is depending on the wining system, which determines whether the individual experiences a state resembling light or darkness. However, the overall mechanism of the competition remains unclear and is expected to be elucidated with future innovations in bioimaging technologies. Immune checkpoint blockade therapy is a means by which the two singularity balances can be artificially manipulated; therefore, mechanistic insight is necessary for cancer treatment strategies. Altogether, these findings provide a different perspective crucial for understanding the behavior of dynamic cell populations in multicellular organisms. [ABSTRACT FROM AUTHOR]

Nanoparticles have been identified in numerous studies as effective antigen delivery systems that enhance immune responses. However, it remains unclear whether this enhancement is a result of increased antigen uptake when carried by nanoparticles or the adjuvanticity of the nanoparticle carriers. Consequently, it is important to quantify antigen uptake by dendritic cells in a manner that is free from artifacts in order to analyze the immune response when antigens are carried by nanoparticles. In this study, we demonstrated several scenarios (antigens on nanoparticles or inside cells) that are likely to contribute to the generation of artifacts in conventional fluorescence-based quantification. Furthermore, we developed the necessary assay for accurate uptake quantification. PLGA NPs were selected as the model carrier system to deliver EsxB protein (a Staphylococcus aureus antigen) in order to testify to the feasibility of the established method. The results showed that for the same antigen uptake amount, the antigen delivered by PLGA nanoparticles could elicit 3.6 times IL-2 secretion (representative of cellular immune response activation) and 1.5 times IL-12 secretion (representative of DC maturation level) compared with pure antigen feeding. The findings above give direct evidence of the extra adjuvanticity of PLGA nanoparticles, except for their delivery functions. The developed methodology allows for the evaluation of immune cell responses on an antigen uptake basis, thus providing a better understanding of the origin of the adjuvanticity of nanoparticle carriers. Ultimately, this research provides general guidelines for the formulation of nano-vaccines. [ABSTRACT FROM AUTHOR]

In this paper, we use terahertz combined with metamaterial technology as a powerful tool to identify analytes at different concentrations. Combined with the microfluidic chip, the experimental measurement can be performed with a small amount of analyte. In detecting the troponin antigen, surface modification is carried out by biochemical binding. Through the observation of fluorescent antibodies, the average number of fluorescent dots per unit of cruciform metamaterial is 25.60, and then, by adjusting the binding temperature and soaking time, the average number of fluorescent dots per unit of cruciform metamaterial can be increased to 181.02. Through the observation of fluorescent antibodies, it is confirmed that the antibodies can be successfully stabilized on the metamaterial and then bound to the target antigen. The minimum detectable concentration is between 0.05~0.1 μg/100 μL, and the concentration and ΔY show a positive correlation of R2 = 0.9909. [ABSTRACT FROM AUTHOR]

The paper reports the assessment of the role of surface antigens in Yersinia pestis adhesion to murine macrophages J774. The ability of Ail and Psa antigens to adhere to eukaryotic cells has been confirmed using optical trapping and/or passive adhesion methods. The YapF autotransporter was shown for the first time to be an adhesin of Y. pestis. It has been suggested that these antigens do not have complementary receptors on the macrophage surface and their adhesive properties are nonspecific. The results of studying passive adhesion of polystyrene microspheres sensitized with the F1 capsular antigen to J774 macrophages suggest that its inhibiting effect on the adhesion to macrophages is determined not only by spatial shielding of underlying adhesins by the capsule but also by physical and chemical properties of the antigen itself. [ABSTRACT FROM AUTHOR]

In preclinical studies, which are conducted to study the therapeutic effectiveness and pharmacological safety of biologically active compounds for the correction of autoimmune thyroiditis, various experimental models of this pathology are used in the experiment. In this work, we analyzed various models of thyroiditis that have been used for the past fifty years. Such an analysis made it possible to choose the most optimal model for the study of autoimmune pathology of the thyroid gland as well as for the correction of this condition. The analysis of known and the search for new pathogenetically justified models of autoimmune diseases of endocrine organs is a very urgent task. The aim of the work was to study the dynamics of changes in the histomorphological structure of the thyroid gland when modeling autoimmune thyroiditis in rats using an allogeneic antigen isolated from the human thyroid gland. The postoperative thyroid gland of a person was used as an antigen. Morphological changes in the thyroid gland were studied one, three and six months after the end of the simulation. It was found that the use of this type of immunization led to changes in the parenchyma of the gland, characteristic of autoimmune thyroiditis. Already one month after modeling, Gürtle cells, fibrosis, areas of lymphoid infiltration of the parenchyma were registered. These pathological changes persisted and worsened three and six months after the end of the simulation. The investigated type of model of experimental autoimmune thyroiditis is easily reproduced. Pathological changes in the gland deepen over time and are comparable to those that occur in people with Hashimoto's thyroiditis. [ABSTRACT FROM AUTHOR]

At present, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is raging worldwide, and the coronavirus disease 2019 outbreak caused by SARS‐CoV‐2 seriously threatens the life and health of all humankind. There is no specific medicine for novel coronavirus yet. So, laboratory diagnoses of novel coronavirus as soon as possible and isolation of the source of infection play a vital role in preventing and controlling the epidemic. Therefore, selecting appropriate detection techniques and methods is particularly important to improve the efficiency of disease diagnosis and treatment and to curb the outbreak of infectious diseases. In this paper, virus nucleic acid, protein, and serum immunology were reviewed to provide a reference for further developing virus detection technology to provide better prevention and treatment strategies and research ideas for clinicians and researchers. Highlights: Laboratory diagnoses of novel coronavirus play a vital role in the whole epidemic situation.Nucleic acid, protein and serum immunoassay of viruses are the main methods.RT‐PCR has become the gold standard for SARS‐CoV‐2 detection because of its high sensitivity and strong specificity. [ABSTRACT FROM AUTHOR]

Clenbuterol is a β-adrenergic receptor agonist that can be used as a bronchodilator for the treatment of respiratory diseases or as an additive feed in livestock to improve conversion rate of lean meat. However, the residue of clenbuterol in food can be a threat to human health. Therefore, it is important to monitor clenbuterol in foods. In this paper, a fluorescence inner filtration immunoassay (FIFI) method for the detection of clenbuterol was developed based on the principle of immunoreactive competitive method and the theory of fluorescence quenching, which was constructed from a fluorescence-quenching detection system and a separation system of magnetic immunization. In the magnetic immunization separation system, the detection antigen competes with the biotin-labeled antigen for binding to colloidal gold-labeled clenbuterol antibody and the immunocomplex is enriched by streptavidin- and biotin-specific reactions on the surface of magnetic beads. The remaining complex as a fluorescence quencher in the detection system after centrifugation, and rhodamine 6G acts as a fluorescence agent. The quantitative detection of clenbuterol was accomplished by achieving fluorescence quenching under excitation light irradiation. The standard solutions of clenbuterol in the range of 0.03–5.0 ng/mL exhibited good correlation (r = 0.9996) with the fluorescence intensity, with limit of detection 0.01 ng/mL and recoveries ranging from 98.1 to 101.2%. Moreover, there was no significant difference between the results obtained after testing valid samples by FIFI and ELISA. Therefore, our developed method is sensitive and efficient, simple to operate, and has great potential for on-site detection of clenbuterol. [ABSTRACT FROM AUTHOR]

A rapid change has been undergone in the current pandemic and many countries are being exposed to the third wave of COVID-19. The tireless work for the discovery of vaccine had begun by the time the disease occupied a major part of the globe. This is mainly due to the efficacy of vaccines in preventing diseases and it is one of the cost effective strategies adopted for the prevention of many diseases. Currently a lot of countries have come forth with suitable vaccines to tackle the SARS CoV-2 to some extent. This paper incorporates details about vaccination and the common vaccines in use against COVID-19. Based on the evidences available, keen observations and studies carried out on the previously emerged SARS and MERS, the vaccine against SARS CoV-2 was developed, however the primary focus depend on the spike protein which was considered as a target for the development of suitable immunotherapies and thereby played a potential role in the vaccine development process. Vaccination is the most significant strategy to stop the pandemic and the efficacy of SARS-CoV-2 vaccines provides a genuine gauge of hope for future. [ABSTRACT FROM AUTHOR]

The polysaccharide mannan is the main surface antigen of the cell wall of Candida fungi, playing an important role in the pathogenesis of diseases caused by these mycopathogens. Mannan has a complex, comb-like structure and includes a variety of structural units, with their combination varying depending on the Candida species and strain. Glucomannan, a polysaccharide from Candida utilis, contains terminal α-d-glucose residues attached to oligomannoside side chains. This paper describes the first synthesis of a pentasaccharide structurally related to C. utilis glucomannan fragment, which is an α-(1→2)-linked tetramannoside terminated at the non-reducing end by an α-d-glucopyranosyl residue. The pentasaccharide was obtained as a 3-aminopropyl glycoside, which made it possible to synthesize also its biotinylated derivative, suitable for various glycobiological studies. The most complicated step in the pentasaccharide synthesis was stereoselective 1,2-cis-glycosylation to attach the α-d-glucopyranosyl residue. This was accomplished using a glucosyl donor specially developed in our laboratory, the protecting groups of which provide the necessary α-stereoselectivity. The target biotinylated pentasaccharide thus obtained will be used in the future as a model antigen for the detection of immunodeterminant epitopes of Candida mannans. [ABSTRACT FROM AUTHOR]

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Introduction: Vaccinations are ideal for reducing the severity of clinical manifestations and secondary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, SARS-CoV-2 continues to cause morbidity and mortality worldwide. In contrast to parenteral vaccines such as messenger RNA vaccines, nasal vaccines are expected to be more effective in preventing viral infections in the upper respiratory tract, the primary locus for viral infection and transmission. In this study,we examined the prospects of an inactivatedwhole-virion (WV) vaccine administered intranasally against SARS-CoV-2. Methods: Mice were immunized subcutaneously (subcutaneous vaccine) or intranasally (nasal vaccine) with the inactivated WV of SARS-CoV-2 as the antigen. Results: The spike protein (S)-specific IgA level was found to be higher upon nasal vaccination than after subcutaneous vaccination. The level of S-specific IgG in the serum was also increased by the nasal vaccine, although it was lower than that induced by the subcutaneous vaccine. The nasal vaccine exhibited a stronger defense against viral invasion in the upper respiratory tract than the subcutaneous vaccine and unimmunized control; however, both subcutaneous and nasal vaccines provided protection in the lower respiratory tract. Furthermore, we found that intranasally administered inactivated WV elicited robust production of S-specific IgA in the nasal mucosa and IgG in the blood of mice previously vaccinated with messenger RNA encoding the S protein. Discussion: Overall, these results suggest that a nasal vaccine containing inactivated WV can be a highly effective means of protection against SARSCoV- 2 infection. [ABSTRACT FROM AUTHOR]

Metal–organic coordination polymers (CPs) are a broad class of materials that include metal–organic frameworks (MOFs). CPs are highly ordered crystalline materials that are composed of metal ions (or metal ion clusters) and multidentate organic ligands that serve as linkers. One‐, two‐, and three‐dimensional CPs can be formed, with 2D and 3D structures referred to as MOFs. CPs have gained a lot of attention due to attractive structural features like structure versatility and tunability, and well‐defined pores that enable the encapsulation of cargo. Further, CPs show a lot of promise for drug delivery applications, but only a very limited number of CPs are currently being evaluated in clinical trials. In this review, we outlined features that are desired for CP‐based drug delivery platform, and briefly described most relevant characterization techniques. We highlighted some of the recent efforts directed toward developing CP‐based drug delivery platforms with the emphasis on vaccines against cancer, infectious diseases, and viruses. We hope this review will be a helpful guide for those interested in the design and evaluation of CP‐based immunological drug delivery platforms. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease [ABSTRACT FROM AUTHOR]

Blood crossmatching is necessary to determine transfusion compatibility between individuals, especially for species for which blood groups have not yet been defined, such as the killer whale (Orcinus orca). This study evaluated methodology for crossmatching in killer whales from a managed care population using individuals of known lineages. Twenty killer whales were evaluated for major or minor crossmatch incompatibilities, determined by evidence of macro‐agglutination. Crossmatching incompatibilities were rarely observed, both when considering 1+ reactions as incompatibilities (~15%; 59/400 pairings with 1+ to 4+) and when omitting 1+ reactions (6%; 24/400 pairings with 2+ to 4+). A universal red blood cell donor within this population (whale T) and universal recipients of red blood cells within this population (whales E, M, O, P, R, S) were identified. Relationships were examined between the most common major crossmatch phenotypes and maternal or paternal lineages. Since these whales have not been previously transfused, the diversity of crossmatch reactions could indicate the presence and diversity of preexisting alloantibodies in killer whale plasma. This study highlights the clinical value of applying a personalized medicine approach to a managed care population. [ABSTRACT FROM AUTHOR]

Skin diseases are a common problem faced by people worldwide, and there is a growing demand for natural and safe solutions to treat them. Nanogels are a promising drug delivery system due to their small size, high surface area, and ability to encapsulate both hydrophilic and hydrophobic compounds. In this study, we aimed to optimize and evaluate the parameters of a herbal-based nanogel formulation for the treatment of skin diseases. The nanogel formulation was prepared using a combination of natural polysaccharides, namely chitosan and sodium alginate, and a herbal extract of neem leaves. The optimization parameters included varying the concentrations of chitosan, sodium alginate, and neem extract, and the pH of the formulation. The optimized formulation was evaluated for its physicochemical properties, drug release profile, stability, and skin irritation potential. The results showed that the optimal nanogel formulation had a particle size of 200 nm, a zeta potential of +25 mV, and a drug entrapment efficiency of 80%. The drug release profile was found to be sustained, with 60% of the drug being released over 8 hours. The stability studies showed that the formulation was stable for 3 months at 4°C. The skin irritation studies indicated that the nanogel formulation was non-irritating and safe for topical application. The herbal-based nanogel formulation developed in this study has the potential to be a safe and effective treatment option for skin diseases. Further studies are required to investigate its efficacy in vivo and in clinical trials. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 was identified as the pathogenic agent causing the COVID-19 pandemic. Among the proteins codified by this virus, the Spike protein is one of the most-external and -exposed. A fragment of the Spike protein, named the receptor binding domain (RBD), interacts with the ACE2 receptors of human cells, allowing the entrance of the viruses. RBD has been proposed as an interesting protein for the development of diagnosis tools, treatment, and prevention of the disease. In this work, a method for recombinant RBD production using Pichia pastoris as a cell factory in a stirred-tank bioreactor (SRTB) up to 7 L was developed. Using a basal saline medium with glycerol, methanol, and compressed air in a four-stage procedure, around 500 mg/L of the raw RBD produced by yeasts (yRBD) and 206 mg/L of purified (>95%) RBD were obtained. Thereby, the proposed method represents a feasible, simple, scalable, and inexpensive procedure for the obtention of RBD for diagnosis kits and vaccines' formulation. [ABSTRACT FROM AUTHOR]

Vaccines trigger an immunological response that includes B and T cells, with B cells producing antibodies. SARS-CoV-2 immunity weakens over time after vaccination. Discovering key changes in antigen-reactive antibodies over time after vaccination could help improve vaccine efficiency. In this study, we collected data on blood antibody levels in a cohort of healthcare workers vaccinated for COVID-19 and obtained 73 antigens in samples from four groups according to the duration after vaccination, including 104 unvaccinated healthcare workers, 534 healthcare workers within 60 days after vaccination, 594 healthcare workers between 60 and 180 days after vaccination, and 141 healthcare workers over 180 days after vaccination. Our work was a reanalysis of the data originally collected at Irvine University. This data was obtained in Orange County, California, USA, with the collection process commencing in December 2020. British variant (B.1.1.7), South African variant (B.1.351), and Brazilian/Japanese variant (P.1) were the most prevalent strains during the sampling period. An efficient machine learning based framework containing four feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, and maximum relevance minimum redundancy) and four classification algorithms (decision tree, k-nearest neighbor, random forest, and support vector machine) was designed to select essential antibodies against specific antigens. Several efficient classifiers with a weighted F1 value around 0.75 were constructed. The antigen microarray used for identifying antibody levels in the coronavirus features ten distinct SARS-CoV-2 antigens, comprising various segments of both nucleocapsid protein (NP) and spike protein (S). This study revealed that S1 + S2, S1.mFcTag, S1.HisTag, S1, S2, Spike.RBD.His.Bac, Spike.RBD.rFc, and S1.RBD.mFc were most highly ranked among all features, where S1 and S2 are the subunits of Spike, and the suffixes represent the tagging information of different recombinant proteins. Meanwhile, the classification rules were obtained from the optimal decision tree to explain quantitatively the roles of antigens in the classification. This study identified antibodies associated with decreased clinical immunity based on populations with different time spans after vaccination. These antibodies have important implications for maintaining long-term immunity to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Immune complexing of target antigen to high affinity host antibody is recognized to impact the sensitivity of commercial heartworm antigen tests. Published information describing the effect of heat on interfering canine host antibodies is lacking. Immune complex dissociation (ICD) by heat treatment of serum for samples initially testing negative for heartworm antigen increases sensitivity of commercial antigen tests, particularly for single sex or low adult infection intensities. In this study the stability and nature of the targeted epitope and mechanism of heat ICD were examined. Methods: Canine IgG was isolated using protein-A columns from serum originating from four dogs evaluated after necropsy: one dog with evidence of previously cleared infection and three dogs with confirmed heartworm infections. These dogs were expected to have an excess of antibodies based on negative antigen test and to have no or low antigen optical density, respectively, following heat treatment. Interference of antigen detection on (non-heated) positive serum was evaluated, following 1:1 mixing of antibody/PBS solutions previously heated at 25 °C, 65 °C, 75 °C, 85 °C, 95 °C and 104 °C, compared to positive serum/PBS control measured by optical density using a commercial heartworm antigen ELISA and protein quantification. Live heartworms incubated in media for 72 h provided excretory/secretory antigen for antigen stability studies following heat, endopeptidase digestion and disulfide bond reduction. Results: Mixing antigen-positive heartworm serum with antibody solutions demonstrated a significant inhibition of antigen detection for antibody solutions previously heated at 25 °C and 65 °C relative to positive serum/PBS control. Antigen detection optical density was restored at or above the control when positive serum was mixed with solutions previously heated at 75 °C, 85 °C, 95 °C and 104 °C. Significant changes occurred in protein levels for antibody solutions heated at 75 °C, 85 °C, 95 °C and 104 °C. Relative stability of antigen from live heartworms in culture was demonstrated following heat, chemical and enzymatic treatment. Conclusions: Significant changes in protein levels and antigen binding ability occurred in IgG solutions heated above 65 °C. The findings confirm heat denaturation of antibodies as the suspected mechanism of heat ICD at 104 °C for antigen diagnosis of heartworm. No significant change occurred in antigen detection following heat, chemical or enzymatic digestions supporting a heat-stable linear nature of the epitope. [ABSTRACT FROM AUTHOR]

In a relatively short period of time new coronavirus disease (COVID-19) has become a global threat, both to human health and to the functioning of human society in general. This pandemic is certainly neither the first nor is it likely to be the last disease episode in human history. At the moment, it is still too early to make a reliable assessment of its total effect on human civilization, but it can already be stated that this disease, and its causative agent SARS-CoV-2 virus, have caused a strong scientific response all around the World. For the first time in this magnitude, it has united the resources of large scientific institutions and companies with the aim of finding solutions for fast and accurate virus detection procedures, effective and safe vaccine, reliable medical treatments, etc. It is astonishing that only a month has passed from the first officially detected case to the complete sequencing of the SARS-CoV-2 virus genome and the creation of the first detection systems based on RT-PCR method. After that, numerous scientific teams and companies worked together, or independently, to improve the detection methods. Their work included further optimization of PCR and other genetic approaches, as well as the development of detection methods based on the analysis of specific antibodies and viral antigens. The aim of this paper is to review the results that were achieved in this area so far, analyze the strategies currently used in the world and the region, and to predict future steps in the process of optimizing and improving methods for SARS CoV-2 detection in individual patients and the global human population. [ABSTRACT FROM AUTHOR]

Rapid antigen tests (RATs) are diagnostic tools developed to specifically detect a certain protein of infectious agents (viruses, bacteria, or parasites). RATs are easily accessible due to their rapidity and simplicity. During the COVID-19 pandemic, RATs have been widely used in detecting the presence of the specific SARS-CoV-2 antigen in respiratory samples from suspected individuals. Here, the authors review the application of RATs as detection tools for COVID-19, particularly in Korea, as well as for several other infectious diseases. To address these issues, we present general knowledge on the design of RATs that adopt the lateral flow immunoassay for the detection of the analyte (antigen). The authors then discuss the clinical utilization of the authorized RATs amidst the battle against the COVID-19 pandemic in Korea and their role in comparison with other detection methods. We also discuss the implementation of RATs for other, non-COVID-19 infectious diseases, the challenges that may arise during the application, the limitations of RATs as clinical detection tools, as well as the possible problem solving for those challenges to maximize the performance of RATs and avoiding any misinterpretation of the test result. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) diagnostics are crucial for proper antenatal and postnatal care and also for surveillance and serosurvey studies. Since the viremia during ZIKV infection is fleeting, serological testing is highly valuable to inform diagnosis. However, current serology tests using whole virus antigens frequently suffer from cross reactivity issues, delays, and technical complexity, especially in low and middle income countries (LMICs) and endemic countries. Here, we describe an indirect ELISA to detect specific IgG antibodies using the ZIKV envelope domain III (EDIII) protein expressed in Drosophila S2 cells as an immunogen. Using a total of 367 clinical samples, we showed that the EDIII-ELISA was able to detect IgG antibodies against ZIKV with high sensitivity of 100.0% and specificity of 94.7% when compared to plaque reduction neutralization tests (PRNTs) as the gold standard and using 0.208 as the cut-off OD value. These results show the usefulness of the recombinant envelope domain III as an alternative to standard whole virus proteins for ZIKV diagnostics as it improves the sensitivity and specificity of IgG ELISA assay when used as an immunogen. This method should, therefore, be extended to serological diagnostic techniques for other members of the flavivirus genus and for use in IgM diagnostic testing. [ABSTRACT FROM AUTHOR]

Several studies have evaluated the serum galactomannan (GM) antigen assay in pediatric patients, and there is convincing evidence for its usefulness as a diagnostic tool for invasive Aspergillus infections in patients with acute leukemias or post allogeneic hematopoietic cell transplantation (HCT). Less is known about the utility of the assay in monitoring responses to treatment in patients with established invasive aspergillosis (IA). Here, we present the long-term kinetics of serum galactomannan in two severely immunocompromised adolescents with invasive pulmonary aspergillosis (IPA) who were cured after complicated clinical courses. We also review the utility of the GM antigen assay in serum as a prognostic tool around the time of diagnosis of IA and as a biomarker to monitor disease activity in patients with established IA and assess responses to systemic antifungal therapy. [ABSTRACT FROM AUTHOR]

Placenta-specific antigens are minimally expressed or unexpressed in normal adult tissues, while they are widely expressed in cancer. In the course of carcinogenesis, a vast array of autoantibodies (AAbs) is produced. Here, we used a quantitative approach to determine the reactivity of AAbs in the sera of patients with breast (BrC: N = 100, 100% female, median age: 51 years), gastric (GC: N = 30, 46.6% female, median age: 57 years), bladder (BC: N = 29, 34.4% female, median age: 57 years), and colorectal (CRC: N = 34, 41.1% female, median age: 51 years) cancers against first-trimester (FTP) and full-term placental proteome (TP) in comparison with age- and sex-matched non-cancer individuals. Human-on-human immunohistochemistry was used to determine reactive target cells in FTP. The effect of pregnancy on the emergence of placenta-reactive autoantibodies was tested using sera from pregnant women at different trimesters of pregnancy. Except for BC, patients with BrC (p < 0.0284), GC (p < 0.0002), and CRC (p < 0.0007) had significantly higher levels of placenta-reactive AAbs. BrC (p < 0.0001) and BC (p < 0.0409) in the early stages triggered higher autoantibody reactivity against FTP. The reactivities of BrC sera with FTP did not show an association with ER, PR, or HER2 expression. Pregnancy in the third trimester was associated with the induction of TP- and not FTP-reactive autoantibodies (=0.018). The reactivity of BrC sera with placental proteins was found to be independent of gravidity or abortion. BrC sera showed a very strong and specific pattern of reactivity with scattered cells beneath the syncytiotrophoblast layer. Our results reinforce the concept of the coevolution of placentation and cancer and shed light on the future clinical application of the placental proteome for the non-invasive early detection and treatment of cancer. [ABSTRACT FROM AUTHOR]

Copyright of Problems of Cryobiology & Cryomedicine / Problemy Kriobiologii i Kriomediciny is the property of National Academy of Sciences of Ukraine Institute for Problems of Cryobiology & Cryomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The roles of antibody and antigen are indispensable in targeted diagnosis, therapy, and biomedical discovery. On top of that, massive numbers of new scientific articles about antibodies and/or antigens are published each year, which is a precious knowledge resource but has yet been exploited to its full potential. We, therefore, aim to develop a biomedical natural language processing tool that can automatically identify antibody and antigen entities from articles. Results: We first annotated an antibody-antigen corpus including 3210 relevant PubMed abstracts using a semi-automatic approach. The Inter-Annotator Agreement score of 3 annotators ranges from 91.46 to 94.31%, indicating that the annotations are consistent and the corpus is reliable. We then used the corpus to develop and optimize BiLSTM-CRF-based and BioBERT-based models. The models achieved overall F1 scores of 62.49% and 81.44%, respectively, which showed potential for newly studied entities. The two models served as foundation for development of a named entity recognition (NER) tool that automatically recognizes antibody and antigen names from biomedical literature. Conclusions: Our antibody-antigen NER models enable users to automatically extract antibody and antigen names from scientific articles without manually scanning through vast amounts of data and information in the literature. The output of NER can be used to automatically populate antibody-antigen databases, support antibody validation, and facilitate researchers with the most appropriate antibodies of interest. The packaged NER model is available at https://github.com/TrangDinh44/ABAG_BioBERT.git. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the sensitivity and specificity of the Panbio™ COVID-19 Ag rapid test device using nasal swabs and those of the SSf-COVID19 kit, one of RT-PCR tests, using saliva specimens. These tests were compared with RT-PCR tests using nasopharyngeal swabs for the diagnosis of SARS-CoV-2 infection. The three diagnostic tests were simultaneously conducted for patients aged ≥ 18 years, who were about to be hospitalized or had been admitted for COVID-19 confirmed by RT-PCR in two research hospitals from August 20 to October 29, 2021. Nasal swabs were tested using the Panbio™ COVID-19 Ag rapid test device. More than 1 mL of saliva was self-collected and tested using the SSf-COVID19 kit. Results: In total, 157 patients were investigated; 124 patients who were about to be hospitalized and 33 patients already admitted for COVID-19. The overall sensitivity and specificity of the Panbio™ COVID-19 Ag rapid test device with nasal swabs were 64.7% (95% confidence interval [CI] 47.9–78.5%) and 100.0% (95% CI 97.0–100.0%), respectively. The median time to confirm a positive result was 180 s (interquartile range 60–255 s). The overall sensitivity and specificity of the SSf-COVID19 kit with saliva specimens were 94.1% (95% CI 80.9–98.4%) and 100.0% (95% CI 97.0–100.0%), respectively. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor T cells (CAR T-cells) are engineered T cells that target tumor-associated antigens. CAR T-cell therapy is a novel developed immunotherapy initially for destroying hematological malignancies. Its great success in clinical practice of hematological malignancies encourages oncologists and scientists to use CAR T-cells for the treatment of solid cancers. However, the efficacy of CAR T-cells in solid tumors is not as good as expected in hematological malignancies. In this review, we summarized the efficacy, safety, and challenges of CAR T-cell therapy in the clinical management of solid tumors. We also discussed the potential strategies currently applied to improve the efficacy and safety of CAR T-cell therapy in solid tumors, and finally prospected the future study direction for CAR T-cell therapy. Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse. Of note, the efficacy of CAR T-cell therapy has been even more disappointing in solid tumors. These challenges mainly include (1) the failures of CAR T-cells to treat highly heterogeneous solid tumors due to the difficulty in identifying unique tumor antigen targets, (2) the expression of target antigens in non-cancer cells, (3) the inability of CAR T-cells to effectively infiltrate solid tumors, (4) the short lifespan and lack of persistence of CAR T-cells, and (5) cytokine release syndrome and neurotoxicity. In combination with these characteristics, the ideal CAR T-cell therapy for solid tumors should maintain adequate T-cell response over a long term while sparing healthy tissues. This article reviewed the status, clinical application, efficacy, safety, and challenges of CAR T-cell therapies, as well as the latest progress of CAR T-cell therapies for solid tumors. In addition, the potential strategies to improve the efficacy of CAR T-cells and prevent side effects in solid tumors were also explored. [ABSTRACT FROM AUTHOR]

Tetracapsuloides bryosalmonae is a malacosporean endoparasite that causes proliferative kidney disease (PKD) in wild and farmed salmonids in Europe and North America. The life cycle of T. bryosalmonae completes between invertebrate bryozoan and vertebrate fish hosts. Inside the fish, virulence factors of T. bryosalmonae are induced during infection or interactions with host cells. T. bryosalmonae genes expressed in vivo are likely to be important in fish pathogenesis. Herein, we identify in vivo induced antigens of T. bryosalmonae during infection in brown trout (Salmo trutta) using in vivo induced antigen technology (IVIAT). Brown trout were exposed to the spores of T. bryosalmonae and were sampled at different time points. The pooled sera were first pre-adsorbed with antigens to remove false positive results. Subsequently, adsorbed sera were used to screen a T. bryosalmonae cDNA phage expression library. Immunoscreening analysis revealed 136 immunogenic T. bryosalmonae proteins induced in brown trout during parasite development. They are involved in signal transduction, transport, metabolism, ion-protein binding, protein folding, and also include hypothetical proteins, of so far unknown functions. The identified in vivo induced antigens will be useful in the understanding of T. bryosalmonae pathogenesis during infection in susceptible hosts. Some of the antigens found may have significant implications for the discovery of candidate molecules for the development of potential therapies and preventive measures against T. bryosalmonae in salmonids. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Biochemistry is the property of Society of Medical Biochemists of Serbia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Coronavirus disease 2019 (COVID-19) is a highly virulent infection that has caused a pandemic since 2019. Early diagnosis of the disease has been recognized as one of the important approaches to minimize the pathological impact and spread of infection. Point-of-care tests proved to be substantial analytical tools, and especially lateral flow immunoassays (lateral flow tests) serve the purpose. In the last few years, biosensors have gained popularity. These are simple but highly sensitive and accurate analytical devices composed from a selective molecule such as an antibody or antigen and a sensor platform. Biosensors would be an advanced alternative to current point-of-care tests for COVID-19 diagnosis and standard laboratory methods as well. Recent discoveries related to point-of-care diagnostic tests for COVID-19, the development of biosensors for specific antibodies and specific virus parts or their genetic information are reviewed. [ABSTRACT FROM AUTHOR]

Secretory IgA plays an important role in the mucosal immune system for protection against pathogens. However, the antigens recognized by these antibodies have only been partially studied. We comprehensively investigated the antigens bound by salivary IgA in healthy adults using microbial protein microarrays. This confirmed that saliva contained IgA antibodies that bind to a variety of pathogenic microorganisms, including spike proteins of severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and other human coronavirus species. Also, many subtypes and strains of influenza virus were bound, regardless of the seasonal or vaccine strains. Salivary IgA also bound many serogroups and serovars of Escherichia coli and Salmonella. Taken together, these findings suggest that salivary IgA, which exhibits broad reactivity, is likely an essential element of the mucosal immune system at the forefront of defense against infection. [ABSTRACT FROM AUTHOR]

The protozoa Leishmania donovani causes visceral leishmaniasis (kala-azar), the third most common vector-borne disease. The visceral organs, particularly the spleen, liver, and bone marrow, are affected by the disease. The lack of effective treatment regimens makes curing and eradicating the disease difficult. The availability of complete L. donovani genome/proteome data allows for the development of specific and efficient vaccine candidates using the reverse vaccinology method, while utilizing the unique sequential and structural features of potential antigenic proteins to induce protective T cell and B cell responses. Such shortlisted candidates may then be tested quickly for their efficacy in the laboratory and later in clinical settings. These antigens will also be useful for designing antigen-based next-generation sero-diagnostic assays. L. donovani's cell surface-associated proteins and secretory proteins are among the first interacting entities to be exposed to the host immune machinery. As a result, potential antigenic epitope peptides derived from these proteins could serve as competent vaccine components. We used a stepwise filtering-based in silico approach to identify the entire surface-associated and secretory proteome of L. donovani, which may provide rationally selected most exposed antigenic proteins. Our study identified 12 glycosylphosphatidylinositol-anchored proteins, 45 transmembrane helix-containing proteins, and 73 secretory proteins as potent antigens unique to L. donovani. In addition, we used immunoinformatics to identify B and T cell epitopes in them. Out of the shortlisted surface-associated and secretory proteome, 66 protein targets were found to have the most potential overlapping B cell and T cell epitopes (linear and conformational; MHC class I and MHC class II). [ABSTRACT FROM AUTHOR]

Rapid antigen detection tests (RADTs) offer advantages over gold‐standard reverse transcription polymerase chain reaction (RT‐PCR) tests in that they are cheaper and provide faster results, thus enabling prompt isolation of positive SARS‐CoV‐2 cases and quarantine of close contacts. The aim of this study was to collate and synthesise empirical evidence on the effectiveness of rapid antigen testing for the screening (including serial testing) and surveillance of asymptomatic individuals to limit the transmission of SARS‐CoV‐2. A rapid review was undertaken in MEDLINE (EBSCO), EMBASE (OVID), Cochrane Library, Europe PMC and Google Scholar up until 19 July 2021, supplemented by a grey literature search. Of the identified 1222 records, 19 reports referring to 16 studies were included. Eight included studies examined the effectiveness of RADTs for population‐level screening, four for pre‐event screening and four for serial testing (schools, a prison, a university sports programme and in care homes). Overall, there is uncertainty regarding the effectiveness of rapid antigen testing for the screening of asymptomatic individuals to limit the transmission of SARS‐CoV‐2. This uncertainty is due to the inconsistent results, the relatively low number of studies identified, the predominantly observational and/or uncontrolled nature of the study designs used, and concerns regarding methodological quality. Given this uncertainty, more real‐world research evidence in relevant settings, which is of good quality and timely, as well as economic evaluation, is required to inform public policy on the widespread use of RADTs in asymptomatic individuals. [ABSTRACT FROM AUTHOR]

Antigen processing and antigen-specific CD8 T cell activation form part and parcel of cell-mediated immunity to infections. Yet, several lacunae remain in our understanding of how antigen processing and CD8 T cell response are coordinated. In this study, using mouse bone marrow-derived dendritic cells (BMDC) as antigen-presenting cells and Ovalbumin (OVA)/DQ-Ovalbumin (DQ-OVA) as model antigen we demonstrated that Wnt5A signaling in BMDC supports antigen processing/presentation and concomitant CD8 T cell activation through regulation of actin and proteasome dynamics. Recombinant Wnt5A conditioning of BMDC and associated actin assembly facilitated DQ-OVA processing, which was inhibited by the proteasome inhibitor MG132. Moreover, Wnt5A depletion led to a significant reduction in OVA processing and presentation. Impaired DQ-OVA processing in Wnt5A depleted BMDC correlated with altered dynamics of both actin and the proteasome regulator PA28α-PA28β, and reduced association of DQ-OVA with actin and proteasome subunits. Inhibited OVA processing/presentation in the Wnt5A depleted BMDC also resulted in subdued activation of OVAsensitized CD8 T cells in co-culture with the BMDC. In concurrence with these findings, we demonstrated reduced OVA processing and impaired CD8 T cell response to OVA immunization in Wnt5A heterozygous mice lacking a copy of the Wnt5A gene in comparison to the wild-type cohorts. Taken together, our results reveal a crucial requirement of Wnt5A signaling in antigen processing/presentation and CD8 T cell activation, thus unveiling a vital regulatory node of cell-mediated immunity, unidentified thus far. [ABSTRACT FROM AUTHOR]

Immunoassays are analytical tools that attract growing research attention in the field of sensors. Among the different analytical methods, the immunoassays based on optical readout have an important role due to the high sensitivity reached in past years by the instrumentation as well as by the preparation of new labels. This review aims to give an overview in term of basic concepts and practical examples of the most used optical immunoassays techniques, in order to help readers to choose the most useful techniques for their analyses. Particular emphasis is dedicated to the application of the presented immunoassays on the detection of the SARS-CoV-2 virus. [ABSTRACT FROM AUTHOR]

Nanovaccine development is a growing research field in which the development of new carriers and bioconjugation approaches is a priority. In this sense, this report describes for the first time, the development of a novel conjugate that consists of gold nanoparticles (AuNPs) obtained by a one-step synthesis using an immunogenic peptide of the Lipopolysaccharide-assembly protein LptD from Vibrio parahaemolyticus bacteria as a reducing and capping agent. The resulting LptD@AuNPs compounds were fully characterized and the results showed the high capacity of the peptide to form complexes and reduce gold ions. The reaction yield estimated was higher than 83% and the chemical integrity of the peptide on the NP surface revealed a tyrosine amino acid bonding on the AuNP surface. Furthermore, the LptD@AuNP system showed high colloidal stability in a wide pH range (3â€"11 pH values), where the hydrodynamic diameter and Zeta potential behavior were strongly influenced by the functional groups of the antigenic peptide. The cytotoxicity assays showed that the obtained system is safe for mouse leukocytes, while immunized mice with LptD@AuNPs produced specific IgG antibodies. These encouraging results revealed the efficacy of some antigenic peptides as reducers and capping agents, in addition, opening the path to determine immunogenicity and immunoprotective efficacy of the LptD@AuNP system against the disease induced by Vibrio parahaemolyticus. [ABSTRACT FROM AUTHOR]

TCR-epitope pair binding is the key component for T cell regulation. The ability to predict whether a given pair binds is fundamental to understanding the underlying biology of the binding mechanism as well as developing T-cell mediated immunotherapy approaches. The advent of large-scale public databases containing TCR-epitope binding pairs enabled the recent development of computational prediction methods for TCR-epitope binding. However, the number of epitopes reported along with binding TCRs is far too small, resulting in poor out-of-sample performance for unseen epitopes. In order to address this issue, we present our model ATM-TCR which uses a multi-head self-attention mechanism to capture biological contextual information and improve generalization performance. Additionally, we present a novel application of the attention map from our model to improve out-of-sample performance by demonstrating on recent SARS-CoV-2 data. [ABSTRACT FROM AUTHOR]

The polymorphic human leukocyte antigen (HLA) system has been considered the main target for alloimmunity, but the non-HLA antibodies and autoimmunity have gained importance in kidney transplantation (KT). Apart from the endothelial injury, secondary self-antigen exposure and the presence of polymorphic alloantigens, respectively, auto- and allo- non-HLA antibodies shared common steps in their development, such as: antigen recognition via indirect pathway by recipient antigen presenting cells, autoreactive T cell activation, autoreactive B cell activation, T helper 17 cell differentiation, loss of self-tolerance and epitope spreading phenomena. Both alloimmunity and autoimmunity play a synergic role in the formation of non-HLA antibodies, and the emergence of transcriptomics and genome-wide evaluation techniques has led to important progress in understanding the mechanistic features. Among them, non-HLA mismatches between donors and recipients provide valuable information regarding the role of genetics in non-HLA antibody immunity and development. [ABSTRACT FROM AUTHOR]