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Many studies have been conducted on measuring avian influenza viruses and their hemagglutinin (HA) antigens via electrochemical principles; most of these studies have used gold electrodes on ceramic, glass, or silicon substrates, and/or labeling for signal enhancement. Herein, we present a paper-based immunosensor for label-free measurement of multiple avian influenza virus (H5N1, H7N9, and H9N2) antigens using flexible screen-printed carbon nanotube-polydimethylsiloxane electrodes. These flexible electrodes on a paper substrate can complement the physical weakness of the paper-based sensors when wetted, without affecting flexibility. The relative standard deviation of the peak currents was 1.88% when the electrodes were repeatedly bent and unfolded twenty times with deionized water provided each cycle, showing the stability of the electrodes. For the detection of HA antigens, approximately 10-μl samples (concentration: 100 pg/ml–100 ng/ml) were needed to form the antigen–antibody complexes during 20–30 min incubation, and the immune responses were measured via differential pulse voltammetry. The limits of detections were 55.7 pg/ml (0.95 pM) for H5N1 HA, 99.6 pg/ml (1.69 pM) for H7N9 HA, and 54.0 pg/ml (0.72 pM) for H9N2 HA antigens in phosphate buffered saline, and the sensors showed good selectivity and reproducibility. Such paper-based sensors are economical, flexible, robust, and easy-to-manufacture, with the ability to detect several avian influenza viruses. [ABSTRACT FROM AUTHOR]

A paper-based electrochemical immunosensor was developed for the detection of cancer antigen 125 (CA125) by screen-printing technique. The reduced graphene oxide/thionine/gold nanoparticles (rGO/Thi/AuNPs) nanocomposites were compounded and coated onto the working electrode of immunosensor for CA125 antibody (anti-CA125) immobilization and detection signal amplification. The detection principle was based on the fact that the immunocomplex formed by specify binding of CA125 antibody and antigen could reduce the current response of thionine, which was proportional to the corresponding concentration of CA125 antigen. The immunoassay results showed that the linear range of CA125 was from 0.1 U mL−1 to 200 U mL−1 with the limit of detection (LOD) of 0.01 U mL−1 at signal to noise of 3. Quality control serum samples measured by our proposed immunosensor showed acceptable agreement with traditional ELISA method with the relative error less than 8.05%. The immunosensor exhibited good electrochemical performance with high reproducibility, reliability, stability and accuracy. The proposed immunosensor could be used for the determination of CA125 and had the potential for point-of-care testing (POCT) of other tumor marker. • A novel electrochemical immunosensor based on rGO/Thi/AuNPs nanocomposites was developed for the determination of CA125. • The rGO/Thi/AuNPs nanocomposites were synthesized to improve the sensitivity of immunosensor. • The immunosensor showed acceptable agreement with traditional ELISA method in clinical diagnosis. • It could be used for point-of-care testing of tumor markers and had the potential for disease screening in remote region. [ABSTRACT FROM AUTHOR]

In this work, we report the development of a general strategy for enhancing the efficiency of target capture in immunoassays, using a bifunctional fusion protein construct which incorporates a substrate-anchoring moiety for the high-abundance immobilization of an antigen-binding domain. This approach was informed by the development of a pseudo first-order rate constant model, and tested in a paper-based assay format using a fusion construct consisting of an rcSso7d binding module and a cellulose-binding domain. These rcSso7d-CBD fusion proteins were solubly expressed and purified from bacteria in high molar yields, and enable oriented, high-density adsorption of the rcSso7d binding species to unmodified cellulose within a 30-second incubation period. These findings were validated using two distinct, antigen-specific rcSso7d variants, which were isolated from a yeast surface display library via flow cytometry. Up to 1.6 micromoles of rcSso7d-CBD was found to adsorb per gram of cellulose, yielding a volume-averaged binder concentration of up to 760 μM within the resulting active material. At this molar abundance, the target antigen is captured from solution with nearly 100% efficiency, maximizing the attainable sensitivity for any given diagnostic system. [ABSTRACT FROM AUTHOR]

Context.--In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program--PCNEO--to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group. Objective.--To report the results from the first 4 years of the PCNEO program. Design.--Program participants were sent 2 sets of challenges per year, each including 1 wet challenge and 2 dry challenges, with associated clinical and laboratory findings. The wet challenges were composed of myeloma cell line specimens (with or without dilution in preserved whole blood) for flow cytometric analysis. The dry (paper) challenges were composed of clinical case summaries and images of flow cytometric test results from various flow cytometry laboratories of committee members. Results.--A total of 116 to 145 laboratories from 17 countries enrolled in the proficiency testing program. For the wet challenges, almost all participants (97%--100%; cumulative, 98.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of undiluted myeloma cell lines. Slightly fewer participants (89.0%--97.4%; cumulative, 95.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of diluted myeloma cell lines (10% or 50% dilutions into peripheral blood) intended to better represent a typical clinical sample. There was generally agreement among 80% or more of participants for positive or negative staining for CD38, CD138, CD19, CD20, and surface and cytoplasmic K and λ light chains. Similarly, 84% to 100% of participants were able to correctly identify the presence of neoplastic plasma cell populations in paper challenges, including the presence of small, neoplastic plasma cell populations (0.01%--5.0% clonal plasma cells) and the presence of nonneoplastic plasma cell populations (correctly identified by 91%--96% of participants). Conclusions.--Participant performance in the new proficiency testing program was excellent overall, with the vast majority of participants able to perform flow cytometric analysis and identify neoplastic plasma cell populations and to identify small plasma cell clones or expanded populations of reactive plasma cells in dry challenge flow cytometry results. This program will allow laboratories to verify the accuracy of their testing program and test interpretations for the assessment of patients suspected of having a plasma cell neoplasm. [ABSTRACT FROM AUTHOR]

A rapid and simple paper-based elution assay for red blood cell antigen typing by the indirect antiglobulin test (IAT) was established. This allows to type blood using IgG antibodies for the important blood groups in which IgM antibodies do not exist. Red blood cells incubated with IgG anti-D were washed with saline and spotted onto the paper assay pre-treated with anti-IgG. The blood spot was eluted with an elution buffer solution in a chromatography tank. Positive samples were identified by the agglutinated and fixed red blood cells on the original spotting area, while red blood cells from negative samples completely eluted away from the spot of origin. Optimum concentrations for both anti-IgG and anti-D were identified to eliminate the washing step after the incubation phase. Based on the no-washing procedure, the critical variables were investigated to establish the optimal conditions for the paper-based assay. Two hundred ten donor blood samples were tested in optimal conditions for the paper test with anti-D and anti-Kell. Positive and negative samples were clearly distinguished. This assay opens up new applications of the IAT on paper including antibody detection and blood donor-recipient crossmatching and extends its uses into non-blood typing applications with IgG antibody-based diagnostics. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

There is currently a lot of interest in the construction of point-of-care devices stemming from paper-based origami biosensors. These devices demonstrate how paper's foldability permits the construction of sensitive, selective, user-friendly, intelligent, and maintainable analytical devices for the detection of several ailments. Herein, the first example of the electrochemical aptasensor-based polyvalent dengue viral antigen detection using the origami paper-folding method is presented. Coupling it with an aptamer leads to the development of a new notation known as OBAs, or origami-based aptasensor, that presents a multitude of advantages to the developed platform, such as assisting in safeguarding the sample from air-dust particles, providing confidentiality, and providing a closed chamber to the electrodes. In this paper, gold-decorated nanocomposites of zinc and graphene oxide (Au/ZnO/GO) were synthesized via the chemical method, and characterization was conducted by Scanning Electron Microscope, Transmission Electron Microscope, UV-Vis, and XRD which reveals the successful formation of nanocomposites, mainly helping to enhance the signal and specificity of the sensor by employing aptamers, since isolation and purification procedures are not required. The biosensor that is being demonstrated here is affordable, simple, and efficient. The reported biosensor is an OBA detection of polyvalent antigens of the dengue virus in human serum, presenting a good range from 0.0001 to 0.1 mg/mL with a limit of detection of 0.0001 mg/mL. The reported single-folding ori-aptasensor demonstrates exceptional sensitivity, specificity, and performance in human serum assays, and can also be used for the POC testing of various viral infections in remote areas and underdeveloped countries, as well as being potentially effective during outbreaks. Highlights: (1) First report on origami-based aptasensors for the detection of polyvalent antigens of DENV; (2) In-house construction of low-cost origami-based setup; (3) Gold-decorated zinc/graphene nanocomposite characterization was confirmed via FESEM/UV-Vis/FTIR; (4) Cross-reactivity of dengue-aptamer has been deduced; (5) Electrochemical validation was conducted through CV. [ABSTRACT FROM AUTHOR]

Abstract: Paper based colorimetric biosensing platform utilizing cross-linked siloxane 3-aminopropyltriethoxysilane (APTMS) as probe was developed for the detection of a broad range of targets including H2O2, glucose and protein biomarker. APTMS was extensively used for the modification of filter papers to develop paper based analytical devices. We discovered when APTMS was cross-linked with glutaraldehyde (GA), the resulting complex (APTMS–GA) displays brick-red color, and a visual color change was observed when the complex reacted with H2O2. By integrating the APTMS–GA complex with filter paper, the modified paper enables quantitative detection of H2O2 through the monitoring of the color intensity change of the paper via software Image J. Then, with the immobilization of glucose oxidase (GOx) onto the modified paper, glucose can be detected through the detection of enzymatically generated H2O2. For protein biomarker prostate specific antigen (PSA) assay, we immobilized capture, not captured anti-PSA antibody (Ab1) onto the paper surface and using GOx modified gold nanorod (GNR) as detection anti-PSA antibody (Ab2) label. The detection of PSA was also achieved via the liberated H2O2 when the GOx label reacted with glucose. The results demonstrated the possibility of this paper based sensor for the detection of different analytes with wide linear range. The low cost and simplicity of this paper based sensor could be developed for “point-of-care” analysis and find wide application in different areas. [Copyright &y& Elsevier]

Highlights: [•] AuNPs on paper were functionalized to develop SERS biodiagnostic platform. [•] Reproducible SERS spectra of antibody–antigen were achieved. [•] Modification of antibody structure upon antigen binding resulted in Raman shifts. [•] SERS intensity increased as a function of antigen concentration. [ABSTRACT FROM AUTHOR]

Simple Summary: The B cell receptor (BCR) is a membrane-bound protein complex that is required for the normal development of B cells. BCR signalling is also involved in the pathogenesis of B cell cancers. While there is substantial literature on genomic analyses of the BCR, there are limited proteomic studies of receptor structure and its interactions with neighbouring proteins. This is partly due to the location of the BCR in the surface-membrane lipid environment that has limited the ability to enrich the complex for proteomic analysis. Here, we report an enrichment technique that can be used for mass spectrometry analyses of the BCR from live B cells. B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes. [ABSTRACT FROM AUTHOR]

The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin®. Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin® and MYL-1401O. In CRA, PBMC stimulated with MYL-1401O or Herceptin® similarly secreted IL-6, TNF-α, IL-1β, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin®, strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals. [ABSTRACT FROM AUTHOR]

Electrochemical paper-based analytical devices (ePADs) are useful analytical devices that serve as point-of-care testing (POCT) devices for various clinical biomarkers in view of their simplicity, portability, and low-cost format. However, multistep reagent manipulation usually restricts the performance of the device for end users. Herein, we developed a sequential ePAD for sequential immunosensing fluid delivery by integrating dual flow behaviors (fast-flow/delayed) within a single paper platform for the simultaneous detection of hepatitis B surface antigen (HBsAg) and hepatitis C core antigen (HCVcAg). In the present work, a fast-flow channel was used for the automated washing of unbound antigens, while a delayed channel was created to store a redox reagent for further electrochemical analysis with a single buffer loading (the analysis time can be completed within 500 s). Hence, the undesirable complex procedure of multi-step reagent manipulation is scarcely needed by the user. The detection limit of the proposed ePAD was as low as 18.2 pg mL−1 for HBsAg and 1.19 pg mL−1 for HCVcAg. In addition, this proposed ePAD was also proven to be effective in real clinical sera from patients to verify its biological applicability. The ePAD sensor shows high promise as an easy-to-use, portable, and extendable sensor for other multiplex biological assays. [Display omitted] • ePAD for simultaneous HBsAg and HCVcAg was created. • First time employment of dual flow behaviors on ePAD for hepatitis markers sensing. • ePAD shows an easy to use, portability, and broad sensing applicability. • The sensor was applied to detect hepatitis markers in real clinical sera. [ABSTRACT FROM AUTHOR]

Demonstration of successful elimination of lymphatic filariasis (LF) in endemic countries requires sensitive diagnostics for accurate definitions of endpoints and future surveillance. There has been interest in complementing available diagnostics with antibody serology testing in children, since negative serology would correspond with cessation of LF transmission. The Filariasis CELISA detects antifilarial IgG4 and has favourable results with serum samples but field application requires an easier sampling method. Ninety-four paired plasma and filter paper samples were assayed with promising results. The filter paper method resultedin a sensitivity of 92% and a specificity of 77% when compared to the paired plasma. One hundred and one filter paper samples were assessed for storage effects. Following 10-month storage at -20°C there was a significant reduction in reactivity (P < .001). Overall the results indicated that filter paper sampling would be a favourable sensitive and specific alternative for blood collection in surveys. [ABSTRACT FROM AUTHOR]

Background: A simple filter paper method was developed for, the transport and storage of monoclonal antibodies (Mabs) at room temperature or -20°C after spotting on filter paper, for subsequent sero-typing of outer membrane antigens of N.meningitidis by dot-blot ELISA. Methods: Monoclonal antibodies (Mabs) were spotted within a 0.5-1 cm diameter area of Whatman grade 903 paper, which were stored individually at room temperature or at -20°C. These MAbs were stored and analyzed after periods of one week, 4 weeks, 12 months, or 13 years in the case of frozen Mab aliquots, or after 4 weeks at -20°C or at room temperature (RT) in the case of Mabs dried on filter paper strips. Assays were performed in parallel using dot-blot ELISA. In addition to the MAbs specific for serotyping class 1, 2 or 3, we used a larger number of Mabs for polysaccharides, lipooligosaccharides (LOS), class 5 and cross-reactive antigens for native outer membrane of N.meningitidis. The Mabs dried on filter paper were eluted with phosphate-buffered saline (PBS) containing 0.2% gelatin. Results: Mabs of the isotypes IgG and IgM dried on filter papers were not affected by duration of storage. The detection by serotyping Mabs was generally consistent for dried filter paper MAb samples stored frozen for over 1 year at -20°C, and although decreased reactive antibody titers were found after storage, this did not interfere with the specificity of the Mabs used after 13 years as dry spots on filter paper. Conclusion: The use of filter paper is an inexpensive and convenient method for collecting, storing, and transporting Mab samples for serotyping studies. In addition, the samples occupy little space and can be readily transported without freezing. The efficiency of using immunoglobulin G (IgG) or M (IgM) eluted was found to be consistent with measurement of IgG or IgM titers in most corresponding, ascites Mabs stored frozen for over 1 year. The application of meningococcal typing methods and designations depend on the question being asked. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a global pandemic outbreak. To date, approximately one million deaths and over 32 million cases have been reported. This ongoing pandemic urgently requires an accurate testing device that can be used in the field in a fast manner. Serological assays to detect antibodies have been proven to be a great complement to the standard method of reverse transcription-polymerase chain reaction (RT-PCR), particularly after the second week of infection. We have developed a specific and sensitive immunosensor for immunoglobulin detection produced against SARS-CoV-2. Unlike other lateral flow-based assays (LFAs) involving the utilization of multiple antibodies, we have reported a label-free paper-based electrochemical platform targeting SARS-CoV-2 antibodies without the specific requirement of an antibody. The presence of SARS-CoV-2 antibodies will interrupt the redox conversion of the redox indicator, resulting in a decreased current response. This electrochemical sensor was proven effective in real clinical sera from patients with satisfactory results. In addition, the proposed format was also extended to antigen detection (the spike protein of SARS-CoV-2), which presents new possibilities for diagnosing COVID-19. • Electrochemical sensor for COVID-19 diagnostic. • Serological assay for SARS-CoV-2 antibodies was demonstrated. • Sensitivity enhancement compared to the traditional LFA devices. • Applicable to real clinical sera with satisfactory results. [ABSTRACT FROM AUTHOR]

A laboratory-based lateral flow (LF) test that utilizes up-converting reporter particles (UCP) for ultrasensitive quantification of Schistosoma circulating anodic antigen (CAA) in urine is a well-accepted test to identify active infection. However, this UCP-LF CAA test requires sample pre-treatment steps not compatible with field applications. Flow, a new low-cost disposable, allows integration of large-volume pre-concentration of urine analytes and LF detection into a single field-deployable device. We assessed a prototype Flow-Schistosoma (Flow-S) device with an integrated UCP-LF CAA test strip, omitting all laboratory-based steps, to enable diagnosis of active Schistosoma infection in the field using urine. Flow-S is designed for large-volume (5–20 mL) urine, applying passive paper-based filtration and antibody-based CAA concentration. Samples tested for schistosome infection were collected from women of reproductive age living in a Tanzania region where S. haematobium infection is endemic. Fifteen negative and fifteen positive urine samples, selected based on CAA levels quantified in paired serum, were analyzed with the prototype Flow-S. The current Flow-S prototype, with an analytical lower detection limit of 1 pg CAA/mL, produced results correlated with the laboratory-based UCP-LF CAA test. Urine precipitates occurred in frozen banked samples and affected accurate quantification; however, this should not occur in fresh urine. Based on the findings of this study, Flow-S appears suitable to replace the urine pre-treatment required for the laboratory-based UCP-LF CAA test, thus allowing true field-based applications with fresh urine samples. The urine precipitates observed with frozen samples, though less important given the goal of testing fresh urines, warrant additional investigation to evaluate methods for mitigation. Flow-S devices permit testing of pooled urine samples with applications for population stratified testing. A field test with fresh urine samples, a further optimized Flow-S device, and larger statistical power has been scheduled. [ABSTRACT FROM AUTHOR]

COVID-19 has evolved into a global pandemic. Early and rapid detection is crucial to control of the SARS-CoV-2 transmission. While representing the gold standard for early diagnosis, nucleic acid tests for SARS-CoV-2 are often complicated and time-consuming. Serological rapid antibody tests are characterized by high rates of false-negative diagnoses, especially during early infection. Here, we developed a novel nanozyme-based chemiluminescence paper assay for rapid and sensitive detection of SARS-CoV-2 spike antigen, which integrates nanozyme and enzymatic chemiluminescence immunoassay with the lateral flow strip. The core of our paper test is a robust Co–Fe@hemin-peroxidase nanozyme that catalyzes chemiluminescence comparable with natural peroxidase HRP and thus amplifies immune reaction signal. The detection limit for recombinant spike antigen of SARS-CoV-2 was 0.1 ng/mL, with a linear range of 0.2-100 ng/mL. Moreover, the sensitivity of test for pseudovirus could reach 360 TCID 50 /mL, which was comparable with ELISA method. The strip recognized SARS-CoV-2 antigen specifically, and there was no cross reaction with other coronaviruses or influenza A subtypes. This testing can be completed within 16 min, much shorter compared to the usual 1-2 h required for currently used nucleic acid tests. Furthermore, signal detection is feasible using the camera of a standard smartphone. Ingredients for nanozyme synthesis are simple and readily available, considerably lowering the overall cost. In conclusion, our paper test provides a high-sensitive point-of-care testing (POCT) approach for SARS-CoV-2 antigen detection, which should greatly facilitate early screening of SARS-CoV-2 infections, and considerably lower the financial burden on national healthcare resources. • Point-of-care antigen tests for screening of SARS-CoV-2 infection were established. • Chemiluminescence improves sensitivity of paper test and benefits early screening. • Nanozyme with high peroxidase activity and stability catalyzes chemiluminescence. • Nanozyme chemiluminescence paper test brings high efficiency and low cost. [ABSTRACT FROM AUTHOR]

In omics sciences, many compounds are measured simultaneously in a sample in a single run. Such analytical performance opens up prospects for improving cellular cancer vaccines and other cell-based immunotherapeutics. This article provides an overview of proteomics technology, known as cell proteomic footprinting. The molecular phenotype of cells is highly variable, and their antigenic profile is affected by many factors, including cell isolation from the tissue, cell cultivation conditions, and storage procedures. This makes the therapeutic properties of cells, including those used in vaccines, unpredictable. Cell proteomic footprinting makes it possible to obtain controlled cell products. Namely, this technology facilitates the cell authentication and quality control of cells regarding their molecular phenotype, which is directly connected with the antigenic properties of cell products. Protocols for cell proteomic footprinting with their crucial moments, footprint processing, and recommendations for the implementation of this technology are described in this paper. The provided footprints in this paper and program source code for their processing contribute to the fast implementation of this technology in the development and manufacturing of cell-based immunotherapeutics. [ABSTRACT FROM AUTHOR]

Background: Vaccination is essential for the prevention of infectious diseases and has helped to reduce disease-related mortality, such as pneumonia. However, traditional vaccine development is time-consuming and risky. Reverse vaccinology (RV) is a promising alternative to developing vaccines based on the in silico discovery of antigens, often termed 'potential vaccine candidates' (PVCs), using a pathogen's proteome. RV prediction technologies, such as VaxiJen (founded in 2007), are used to take the first step toward vaccine development. VaxiJen is used by researchers to identify PVCs for various diseases. A 10-year review of these PVCs was published in 2017. There has since been no review of viral PVCs predicted by VaxiJen from 2017 to 2021. The proposed scoping review aims to address this gap. Methods: This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 checklist. The review will employ Arksey and O'Malley's five-stage methodological framework, which was later enhanced by Levac et al. and the Joanna Briggs Institute (JBI). The PRISMA extension for Scoping Reviews (PRISMA-ScR) reporting guideline will be utilized with this framework. PubMed, Scopus, Web of Science, EBSCOhost, and ProQuest One Academic will be searched using the term 'vaxijen'. The inclusion criteria will be English-only full-text original articles published in peer-reviewed journals and unpublished papers from 2017 to 2021. Rayyan will be used to deduplicate, screen titles and abstracts of articles. The articles' full texts will be examined. The data will be extracted using Microsoft Excel. Using a data charting form, data will be sifted and organized by key categories and themes. Discussion: This protocol was submitted for publication and went through an extensive peer review process. The review has implications for novel vaccine development against various viruses. The key limitation of this study is language bias due to the selection of English-only papers because of limited resources. This study will not require ethical clearance since it will use secondary data and will not include patients. Nevertheless, this research is part of a larger project that was submitted for ethical consideration to the Biomedical Research Ethics Committee of the University of KwaZulu-Natal in South Africa. This study's findings will be published in a peer-reviewed journal and provided to relevant stakeholders. Systematic review registration: Open Science Framework (OSF): https://osf.io/ht8wr [ABSTRACT FROM AUTHOR]

Simple Summary: This paper aims at showing the impact of novel imaging technologies and modern radiotherapy techniques on the management of cancer, with a particular focus on prostate adenocarcinoma. The manuscript explores the value of diagnostic imaging before treatment, the role of radiomics in predicting outcomes, the benefit of novel imaging in radiotherapy planning and the influence of advanced technologies in systemic treatment and in the management of other non-oncological conditions in order to tailor the best therapeutical strategies. Introduction: Targeted dose-escalation and reduction of dose to adjacent organs at risk have been the main goal of radiotherapy in the last decade. Prostate cancer benefited the most from this process. In recent years, the development of Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) radically changed clinical practice, also thanks to the availability of modern imaging techniques. The aim of this paper is to explore the relationship between diagnostic imaging and prostate cancer radiotherapy techniques. Materials and Methods: Aiming to provide an overview of the integration between modern imaging and radiotherapy techniques, we performed a non-systematic search of papers exploring the predictive value of imaging before treatment, the role of radiomics in predicting treatment outcomes, implementation of novel imaging in RT planning and influence of imaging integration on use of RT in current clinical practice. Three independent authors (GF, IM and ID) performed an independent review focusing on these issues. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used, and grey literature was searched for further papers of interest. The final choice of papers included was discussed between all co-authors. Results: This paper contains a narrative report and a critical discussion of the role of new modern techniques in predicting outcomes before treatment, in radiotherapy planning and in the integration with systemic therapy in the management of prostate cancer. Also, the role of radiomics in a tailored treatment approach is explored. Conclusions: Integration between diagnostic imaging and radiotherapy is of great importance for the modern treatment of prostate cancer. Future clinical trials should be aimed at exploring the real clinical benefit of complex workflows in clinical practice. [ABSTRACT FROM AUTHOR]

Cancer antigen 15–3 (CA 15-3) is a crucial marker used in the diagnosis and monitoring of breast cancer (BC). The demand for early and precise cancer detection has grown, making the creation of biosensors that are highly sensitive and specific essential. This review paper provides a thorough examination of the progress made in optical and electrochemical biosensors for detecting the cancer biomarker CA 15-3. We focus on explaining their fundamental principles, sensitivity, specificity, and potential for point-of-care applications. The performance attributes of these biosensors are assessed by considering their limits of detection, reaction times, and operational stability, while also making comparisons to conventional methods of CA 15-3 detection. In addition, we explore the incorporation of nanomaterials and innovative transducer components to improve the performance of biosensors. This paper conducts a thorough examination of recent studies to identify the existing obstacles. It also suggests potential areas for future research in this fast progressing field.The paper provides insights into their advancement and utilization to enhance patient outcomes. Both categories of biosensors provide significant promise for the detection of CA 15-3 and offer distinct advantages compared to conventional analytical approaches. [Display omitted] • Identification of CA15-3 cancer biomarker can be done with aptamer-based biosensors • Further research needs to be carried out to use them in point-of-care diagnostics • Nanoaptasensors show very low detection limits and are used for in vivo detection • Their toxicity needs to be evaluated prior to their application in clinical diagnosis [ABSTRACT FROM AUTHOR]

Simple Summary: In this paper, we report on the inhibition of glioblastoma (GBM) cell growth and migration by the putative S1PR1 modulator ACT-2009905, using appropriate in vitro models. This work is based on our previously published finding that S1PR1 expression is strongly up-regulated in human glioblastoma samples and the fact that there is an association between S1PR1 with patients' survival times. We now show that pharmacological modulation by the putative S1PR1 modulator ACT-209905 inhibits GBM cell growth and migration. Furthermore, we investigated the influence of co-culture of GBM cells with THP-1 cells as a model for human monocytes, showing pro-tumoral effects and arguing for a complex interplay between GBM cells, immune cells and underlying signaling pathways. We believe that this manuscript fits the interests of the readership of the journal Cancers as it addresses the impact of alternative therapeutic options using ACT-209905 for improving GBM therapy. Glioblastoma (GBM) is still a deadly tumor due to its highly infiltrative growth behavior and its resistance to therapy. Evidence is accumulating that sphingosine-1-phosphate (S1P) acts as an important tumor-promoting molecule that is involved in the activation of the S1P receptor subtype 1 (S1PR1). Therefore, we investigated the effect of ACT-209905 (a putative S1PR1 modulator) on the growth of human (primary cells, LN-18) and murine (GL261) GBM cells. The viability and migration of GBM cells were both reduced by ACT-209905. Furthermore, co-culture with monocytic THP-1 cells or conditioned medium enhanced the viability and migration of GBM cells, suggesting that THP-1 cells secrete factors which stimulate GBM cell growth. ACT-209905 inhibited the THP-1-induced enhancement of GBM cell growth and migration. Immunoblot analyses showed that ACT-209905 reduced the activation of growth-promoting kinases (p38, AKT1 and ERK1/2), whereas THP-1 cells and conditioned medium caused an activation of these kinases. In addition, ACT-209905 diminished the surface expression of pro-migratory molecules and reduced CD62P-positive GBM cells. In contrast, THP-1 cells increased the ICAM-1 and P-Selectin content of GBM cells which was reversed by ACT-209905. In conclusion, our study suggests the role of S1PR1 signaling in the growth of GBM cells and gives a partial explanation for the pro-tumorigenic effects that macrophages might have on GBM cells. [ABSTRACT FROM AUTHOR]

Simple Summary: The frequency of metastatic melanoma, an extremely deadly malignancy, is rapidly increasing worldwide. Recently, messenger RNA (mRNA) injections have emerged as a promising treatment option. While mRNA therapies have demonstrated significant promise, the stability of the naked form remains a barrier, as naked mRNAs are vulnerable to common ribonucleases, and are unable to effectively penetrate plasma membranes and escape from endosomes. Thus, for this paper, we used a hyper-branched cyclodextrin-based polymer (Ppoly) as a carrier to enhance mRNA delivery for melanoma cancer. The in vitro results demonstrated that Ppoly was able to deliver the EGFP-mRNA effectively in both 2D and 3D melanoma cell lines compared to naked mRNA; in addition, Ppoly did not show any cytotoxicity. The anti-tumour effect of intratumourally injected OVA-mRNA loaded on Ppoly results showed a significant decrease in both tumour size and weight compared to other formulations by inducing an efficient adaptive immune response and OVA-specific CD8+ T cells in both spleen and tumour tissues compared to other groups. mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer. We found that the transfection efficacy of the mRNA-EGFP-loaded Ppoly system was significantly higher than that of lipofectamine and free mRNA in both 2D and 3D melanoma cancer cells; also, this delivery system did not show cytotoxicity. In addition, the biodistribution results revealed time-dependent and significantly higher mEGFP expression in complexes with Ppoly compared to free mRNA. We then checked the anti-tumour effect of intratumourally injected free mRNA–OVA, a foreign antigen, and loaded Ppoly; the results showed a considerable decrease in both tumour size and weight in the group treated with OVA-mRNA in loaded Ppoly compared to other formulations with an efficient adaptive immune response by dramatically increasing most leukocyte subtypes and OVA-specific CD8+ T cells in both the spleen and tumour tissues. Collectively, our findings suggest that the local delivery of cationic cyclodextrin-based polymer complexes containing foreign mRNA antigens might be a good and reliable concept for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

This paper outlines methods used to identify novel antigens for use in the development of serological assays. Specifically, we applied these methods to a neurogenic parasitic nematode of cervids called Parelaphostrongylus tenuis. This parasite is of particular concern in both wild and domestic ungulates as it causes significant neurological signs and definitive diagnosis is only possible post-mortem, necessitating the development of serologic assays for antemortem diagnosis. Proteins extracted from P. tenuis organisms were affinity isolated using antibodies enriched from seropositive moose (Alces alces). The proteins were analyzed using mass spectrometry and liquid chromatography to obtain amino acid sequences that were then cross-referenced to open reading frames predicted from an assembled transcriptome. An antigen of interest was assessed for immunogenic epitopes and subsequently synthesized into 10-mer synthetic overlapping peptides representing these regions. These synthetic peptides were then assessed for reactivity against positive and negative moose sera and demonstrated potential use as a serological assay in diagnostic laboratories. Known negative moose sera revealed significantly lower optical density when compared to the positive samples (p < 0.05). This method serves as a pipeline for the construction of diagnostic assays of pathogens in both human and veterinary medicine. [ABSTRACT FROM AUTHOR]

There are no assays for detecting B. burgdorferi antigen in blood of infected Lyme disease individuals. Here, we provide proof-of-principle evidence that we can quantify B. burgdorferi antigen in spiked blood using a portable smartphone-based fluorescence microscope that measures immunoagglutination on a paper microfluidic chip. We targeted B. burgdorferi OspA to develop a working prototype and added examples of two antigens (OspC and VlsE) that have diagnostic value for discrimination of Lyme disease stage. Using an extensively validated monoclonal antibody to OspA (LA-2), detection of OspA antigen had a broad linear range up to 100 pg/mL in 1% blood and the limit of detection (LOD) was 100 fg/mL (= 10 pg/mL in undiluted blood), which was 1000 times lower than our target of 10 ng/mL. Analysis of the two other targets was done using polyclonal and monoclonal antibodies. OspC antigen was detected at LOD 100 pg/mL (= 10 ng/mL of undiluted blood) and VlsE antigen was detected at LOD 1–10 pg/mL (= 0.1–1 ng/mL of undiluted blood). The method is accurate and was performed in 20 min from sample to answer. When optimized for detecting several B. burgdorferi antigens, this assay may differentiate active from past infections and facilitate diagnosis of Lyme disease in the initial weeks of infection, when antibody presence is typically below the threshold to be detected by serologic methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiolabeled choline and PSMA PET have been largely tested in the initial staging of prostate cancer and for biochemical recurrence. Moreover, diverse data are now available about their role in the evaluation of response to local and systematic therapies, and their predictive impact on the prognosis, before and after therapy. Therefore, in the present systematic review, we aimed to describe the available data, to summarize the current evidence in these settings of disease. The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and survival outcomes in prostate cancer. We performed a systematic literature search in PubMed/Scopus/Google Scholar/Cochrane/EMBASE databases (between January 2010 and October 2021) accordingly. The quality of the included studies was evaluated following the "Quality Assessment of Prognostic Accuracy Studies" tool (QUAPAS-2). We selected 40 articles: 23 articles discussed the use of PET imaging with [68Ga]PSMA-11 (16 articles/1123 patients) or [11C]/[18F]Choline (7 articles/356 patients) for the prediction of response to radiotherapy (RT) and survival outcomes. Seven articles (three with [68Ga]PSMA-11, three with [11C]Choline, one with [18F]Choline) assessed the role of PET imaging in the evaluation of response to docetaxel (as neoadjuvant therapy in one study, as first-line therapy in five studies, and as a palliative regimen in one study). Seven papers with radiolabeled [18F]Choline PET/CT (n = 121 patients) and three with [68Ga]PSMA-11 PET (n = 87 patients) were selected before and after enzalutamide/abiraterone acetate. Finally, [18F]Choline and [68Ga]PSMA-11 PET/CT as gatekeepers for the treatment of metastatic prostate cancer with Radium-223 were assessed in three papers. In conclusion, in patients undergoing RT, radiolabeled choline and [68Ga]PSMA-11 have an important prognostic role. In the case of systemic therapies, the role of such new-generation imaging techniques is still controversial without sufficient data, thus requiring additional in this scenario. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most prevalent cerebral cancer in adults without proven therapy. Chimeric antigen receptor T cell treatment has demonstrated good clinical success in hematologic cancers. The application of chimeric antigen receptor T cell therapy to solid tumors, such as glioblastoma, is currently the subject of scientific investigation. The creation of chimeric antigen receptor T cells and its iterations are briefly described in this article. Specifically, this study addresses the obstacles and hurdles faced and glioblastoma targets studied in recent years. This review provides the reader with a comprehensive understanding of the current state of chimeric antigen receptor T cell therapy for glioblastoma and a clear understanding of each therapeutic target. Glioblastoma (GBM) is an aggressive primary brain tumor with a poor prognosis following conventional therapeutic interventions. Moreover, the blood–brain barrier (BBB) severely impedes the permeation of chemotherapy drugs, thereby reducing their efficacy. Consequently, it is essential to develop novel GBM treatment methods. A novel kind of pericyte immunotherapy known as chimeric antigen receptor T (CAR-T) cell treatment uses CAR-T cells to target and destroy tumor cells without the aid of the antigen with great specificity and in a manner that is not major histocompatibility complex (MHC)-restricted. It has emerged as one of the most promising therapy techniques with positive clinical outcomes in hematological cancers, particularly leukemia. Due to its efficacy in hematologic cancers, CAR-T cell therapy could potentially treat solid tumors, including GBM. On the other hand, CAR-T cell treatment has not been as therapeutically effective in treating GBM as it has in treating other hematologic malignancies. CAR-T cell treatments for GBM have several challenges. This paper reviewed the use of CAR-T cell therapy in hematologic tumors and the selection of targets, difficulties, and challenges in GBM. [ABSTRACT FROM AUTHOR]

AIMS: This review is focused on the laboratory diagnoses of the coronavirus disease 2019 (COVID-19) by recognizing the antigen of the causative agent SARS-CoV-2 virus. Various antigen tests are available in this moment and these tests are being further developed in order to reach a better diagnostic value. The issue is reviewed in a complex view. METHODS: In this work, a complex survey of the current literature was made. The relevant and recent papers related to antigen tests of COVID-19 are discussed and cited. Basic specifications of the antigen tests and competitive methods were also scrutinized in the current literature. RESULTS: The survey of the current literature (years 2019 - 2021) was made and diagnostic methods like lateral flow tests (lateral flow immunochromatographic assay) and various types of biosensors were specified as tools for COVID-19 diagnosis and their application to be used as a point-of-care test is considered. CONCLUSIONS: Small hand-held assays applicable in the point-of-care conditions for diagnosis of COVID-19 by analysis of SARS-CoV-2 antigen are the means of a growing interest and these means undergo a significant development leading to the improvements of their specifications and applicability to the current praxis. Merit of the assays is discussed in this paper. [ABSTRACT FROM AUTHOR]

The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse. [ABSTRACT FROM AUTHOR]

This paper aimed to investigate the influence of polymorphisms in the FCGR2A gene encoding R131H FcgRIIA variants and in the FCGR3B gene (108G > C, 114C > T, 194 A > G, 233C > A, 244 G > A and 316G > A) encoding FcgRIIIB-NA1, -NA2 and -SH variants on malaria susceptibility and antibody responses against P. falciparum merozoite antigens in Beninese children. An active malaria follow-up was conducted in infants from birth to 24 months of age in Allada, Benin. FCGR3B exon 3 was sequenced and FCGR2A exon 4 was genotyped. Antibodies directed to GLURP and MSP3 were quantified by ELISA. Association studies were performed using mixed-effect models. Individual carriage of FCGR3B 194 AA genotype was associated with a high number of malaria infections and a low level of IgG1 against MSP3 and GLURP-R0. High parasitemia and increased malaria infections were observed in infants carrying the FCGR3B*05 108C-114T-194A-233C-244A-316A haplotype. A reduced risk of malaria infections and low parasitemia were related to the carriages of the FCGR3B 108C-114T-194G-233C-244G-316A (FCGR3B*06), FCGR3B 108C–114T–194G–233A–244A–316A (FCGR3B*03 encoding for FcgRIIIB-SH) haplotypes and FCGR3B 297 TT genotype. Our results highlight the impact of FCGR3B polymorphisms on the individual susceptibility to malaria and antibody responses against MSP3 and GLURP in Beninese children. [ABSTRACT FROM AUTHOR]

Simple Summary: Haemonchus contortus is the most pathogenic blood-feeding parasitic nematode in sheep and goats, threatening animal welfare and causing tremendous economic losses to the small ruminant industry. This comprehensive review article sums up current control strategies, worm-derived antigens and recent advances in anti-Haemonchus vaccine development. New insights into antigen engineering and general considerations for clinical trials are discussed here. The evolutionary success of parasitic worms causes significant economic losses and animal health problems, including in the small ruminant industry. The hematophagous nematode Haemonchus contortus is a common endoparasite that infects wild and domestic ruminants worldwide, especially in tropical and subtropical regions. To date, the most commonly applied control strategy is the administration of anthelminthic drugs. The main disadvantages of these chemicals are their ecotoxic effects, the necessary withdrawal period (especially important in dairy animals) and the increasing development of resistance. Vaccines offer an attractive alternative control strategy against Haemonchus infections. In previous years, several potential vaccine antigens prepared from H. contortus using the latest technologies have been assessed in clinical trials using different methods and strategies. This review highlights the current state of knowledge on anti-H. contortus vaccines (covering native, recombinant and DNA-based vaccines), including an evaluation, as well a discussion of the challenges and achievements in developing protective, efficient, and long-lasting vaccines to control H. contortus infection and haemonchosis in small ruminants. This paper also addresses novel developments tackling the challenge of glycosylation of putative candidates in recombinant form. [ABSTRACT FROM AUTHOR]

T-cell intracellular antigen 1 (TIA1)-related/like (TIAR/TIAL1) protein is a multifunctional RNA-binding protein (RBP) involved in regulating many aspects of gene expression, independently or in combination with its paralog TIA1. TIAR was first described in 1992 by Paul Anderson's lab in relation to the development of a cell death phenotype in immune system cells, as it possesses nucleolytic activity against cytotoxic lymphocyte target cells. Similar to TIA1, it is characterized by a subcellular nucleo-cytoplasmic localization and ubiquitous expression in the cells of different tissues of higher organisms. In this paper, we review the relevant structural and functional information available about TIAR from a triple perspective (molecular, cellular and pathophysiological), paying special attention to its expression and regulation in cellular events and processes linked to human pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment. Methodology/Principal findings: We identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a single exon that encodes a 16.3 kD protein (Wb-Bhp-1) with 45% amino acid identity to BmR1. Immunohistology shows that anti-Wb-Bhp-1 antibodies primarily bind to Mf. Plasma from 124 of 224 (55%) microfilaremic individuals had IgG4 antibodies to Wb-Bhp-1 by ELISA. Serologic reactivity to Wb-Bhp-1 varied widely with samples from different regions (sensitivity range 32–92%), with 77% sensitivity for 116 samples collected from microfilaremic individuals outside of sub-Saharan Africa. This variable sensitivity highlights the importance of validating new diagnostic tests for parasitic diseases with samples from different geographical regions. Individuals with higher Mf counts were more likely to have anti-Wb-Bhp-1 antibodies. Cross-reactivity was observed with a minority of plasma samples from people with onchocerciasis (17%) or loiasis (10%). We also identified, cloned and characterized BmR1 homologues from O. volvulus and L. loa that have 41% and 38% identity to BmR1, respectively. However, antibody assays with these antigens were not sensitive for onchocerciasis or loiasis. Conclusions: Wb-Bhp-1 is a novel antigen that is useful for serologic diagnosis of bancroftian filariasis. Additional studies are needed to assess the value of this antigen for monitoring the success of filariasis elimination programs. Author summary: Lymphatic filariasis (LF) is a highly disabling and stigmatizing disease caused by parasitic worms that are transmitted by mosquitoes. There is a coordinated global effort to eliminate LF based on mass drug administration (MDA) of donated anti-filarial medications. Improved methods are needed to determine when transmission of the infection has been interrupted in previously endemic areas so that MDA can be safely stopped. This paper reports the discovery and characterization of a novel W. bancrofti antigen, Wb-Bhp-1, which is a homologue of the Brugia malayi protein used in antibody tests to monitor filariasis elimination in areas of Asia where LF is caused by Brugia species. We show that a test for IgG4 antibodies to Wb-Bhp-1 was fairly specific for W. bancrofti infection. However, the sensitivity of this test varied by the geographic origin of the samples. Sensitivity was highest for samples collected in the Indo-Pacific region and lowest for samples collected in Côte d'Ivoire. Geographic differences in the parasite or the human immune responses to infection may account for this variability. This range in sensitivity highlights the importance of validating new diagnostic tests for parasitic diseases with samples from different geographical regions. [ABSTRACT FROM AUTHOR]

The creation of cancer vaccines is a constant priority for research and biotechnology. Therefore, the emergence of any new technology in this field is a significant event, especially because previous technologies have not yielded results. Recently, the development of a cancer vaccine has been complemented by a new proteomics technology platform that allows the creation of antigen compositions known as antigenic essences. Antigenic essence comprises a target fraction of cellular antigens, the composition of which is precisely controlled by peptide mass spectrometry and compared to the proteomic footprint of the target cells to ensure similarity. This proteomics platform offers potential for a massive upgrade of conventional cellular cancer vaccines. Antigenic essences have the same mechanism of action, but without the disadvantages, and with notable advantages such as precise targeting of the immune response, safety, controlled composition, improved immunogenicity, addressed MHC restriction, and extended range of vaccination doses. The present paper calls attention to this novel platform, stimulates discussion of the role of antigenic essence in vaccine development, and consolidates academic science with biotech capabilities. A brief description of the platform, list of cellular cancer vaccines suitable for the upgrade, main recommendations, limitations, and legal and ethical aspects of vaccine upgrade are reported here. [ABSTRACT FROM AUTHOR]

Supply shortage for the development and production of preventive, therapeutic, and diagnosis tools during the COVID-19 pandemic is an important issue affecting the wealthy and poor nations alike. Antibodies and antigens are especially needed for the production of immunological-based testing tools such as point-of-care tests. Here, we propose a simple and quick magnetic nanoparticle (MNP)–based separation/isolation approach for the repurposing of infected human samples to produce specific antibodies and antigen cocktails. Initially, an antibody cocktail was purified from serums via precipitation and immunoaffinity chromatography. Purified antibodies were conjugated onto MNPs and used as an affinity matrix to separate antigens. The characterization process was performed by ELISA, SDS-PAGE, electrochemistry, isothermal titration calorimetry, and LC-Q-TOF-MS/MS analyses. The MNP-separated peptides can be used for mass spectrometry–based as well as paper-based lateral flow assay diagnostic. The exploitation of the current workflow for the development of efficient diagnostic tools, specific treatments, and fundamental research can significantly impact the present or eventual pandemic. This workflow can be considered as a two birds, one stone–like strategy. [ABSTRACT FROM AUTHOR]

The article comments on a paper by B. Magnani and C. R. Taylor on the regulation of immunohistochemistry (IHC) as an assay. Topics mentioned include the challenges for achieving accuracy and precision with IHC, the impact of signal detection on how IHC and immunoassay should be regulated by government agencies in the U.S., the need to incorporate clinical immunoassay concepts into the IHC laboratory, and some developments in the staining/technical aspects of IHC.

Treatment failure or relapse due to tumor escape caused by reduction in target antigen expression has become a challenge in the field of CART therapy. Target antigen density is closely related to the effectiveness of CART therapy, and reduced or lost target antigen expression limits the efficacy of CART therapy and hinders the durability of CAR T cells. Epigenetic drugs can regulate histones for molecular modifications to regulate the transcriptional, translational and post-translational modification processes of target agents, and we demonstrated for the first time the role in regulating CD22 expression and its effect on the efficacy of CD22 CART. In this paper, we found that Chidamide promoted the expression of CD22 on the surface of B-cell tumor cells in vitro and in vivo, and enhanced the function of CD22 CART. As for mechanisms, we demonstrated that Chidamide did not affect CD22 mRNA transcription, but significantly increased the expression of total CD22 protein, indicating that Chidamide may upregulate cell surface CD22 expression by affecting the distribution of CD22 protein. In summary, our results suggest that Chidamide may enhance the efficacy of CD22 CART by inhibiting histone deacetylases to regulate post-transcriptional modifications that affect protein distribution to increase the expression of CD22 on the cell surface. [ABSTRACT FROM AUTHOR]

Lymphatic filariasis (LF) is a parasitic disease caused by the worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. It is a tropical and subtropical illness that affects approximately 67 million people worldwide and that still requires better diagnostic tools to prevent its spread and enhance the effectiveness of control procedures. Traditional parasitological tests and diagnostic methods based on whole protein extracts from different worms are known for problems related to sample time collection, sensitivity, and specificity. More recently, new diagnostic tools based on immunological methods using recombinant antigens have been developed. The current review describes the several recombinant antigens used as tools for lymphatic filariasis diagnosis in antigen and antibody capture assays, highlighting their advantages and limitations as well as the main commercial tests developed based on them. The literature chronology is from 1991 to 2021. First, it describes the historical background related to the identification of relevant antigens and the generation of the recombinant polypeptides used for the LF diagnosis, also detailing features specific to each antigen. The subsequent section then discusses the use of those proteins to develop antigen and antibody capture tests to detect LF. So far, studies focusing on antibody capture assays are based on 13 different antigens with at least six commercially available tests, with five proteins further used for the development of antigen capture tests. Five antigens explored in this paper belong to the SXP/RAL-2 family (BmSXP, Bm14, WbSXP-1, Wb14, WbL), and the others are BmShp-1, Bm33, BmR1, BmVAH, WbVAH, BmALT-1, BmALT-2, and Wb123. It is expected that advances in research with these antigens will allow further development of tests combining both sensitivity and specificity with low costs, assisting the Global Program to Eliminate Lymphatic Filariasis (GPELF). [ABSTRACT FROM AUTHOR]

This paper proposes MAGE — A Malware Antigen Generating Evolutionary algorithm that is capable of generating unseen variants of a given source malware. MAGE evolves malware variants by employing code transformation functions as mutation operators and intra-population Jaccard similarity metric as fitness function. By virtue of these design choices, MAGE is capable of generating active malware variants with diverse code structure variations while retaining the maliciousness of the source malware. These malware variants (similar to biological antigens) generated throughout the run of MAGE forms a potential dataset of malware variants. The dataset can be used to train an adaptive Antivirus engine to learn the code structure variations that make up the space of malware variants. This could augment the engines ability to detect unseen malware variants, thus preventing attacks from the same. The efficacy of MAGE has been demonstrated with two malware viz. Timid , a COM infector and Intruder , an EXE infector. The simulation experiments demonstrate the potential and versatility of MAGE towards generating diverse malware variants. • This paper proposes a malware antigen generating evolutionary algorithm (MAGE). • MAGE is capable of generating variants of a given malware as Antigens for antivirus. • The evolved malware successfully evade detection by over 97 • MAGE evolves diverse non-trivial assembly code structure variations from source. • The evolved variants retain their original malicious characteristics. • The variants evolved can be fed to adaptive antivirus engines to prevent infection. [ABSTRACT FROM AUTHOR]

Based on the pathohistological examination of tonsillar tissue, chronic tonsillitis can be classified as chronic hypertrophic tonsillitis (CHT) and recurrent tonsillitis (RT). CD68 is a glycoprotein ubiquitously expressed on the cells of the monocyte-macrophage lineage, as well as on the dendritic cells. Macrophages and dendritic cells are major initiators, effectors, and regulators of immune response in the palatine tonsil. The aim of this paper was to examine microanatomical distribution of CD68-immunopositive cells and to determine their numerical areal density in morphological compartments of palatine tonsils with CHT and RT, in order to show the possible differences in antigen-presentation potential between these two pathological conditions. As a material we used tonsils taken after tonsillectomy, from patients of both sexes, aged 10-29 years: six tonsils with RT and nine tonsils with CHT. The quantification of CD68- immunopositive cells by "ImageJ" software was performed on 5 µm thick serial paraffin tissue slices, which were stained immunohistochemically, by using monoclonal anti-CD68 antibody. The results of morphometrical analysis showed presence of CD68-immunopositive cells in all morphological compartments of tonsils with RT and CHT, being higher in number in RT compared with CHT. Statistically significant difference in numerical areal density of the CD68- immunopositive cells was found in the germinal centers of lymphoid follicles (RT > CHT), and interfollicular lymphoid tissue (CHT > RT). The difference in the number of CD68-immunopositive cells might imply the different mechanisms involved in the infiltration of tonsillar tissue with CD68-immunopositive cells, as well as the different antigen-presenting potential in these two conditions. [ABSTRACT FROM AUTHOR]

This paper describes a convenient and straightforward method developed to extract keratin particles (KPs) from human hair. It also involves their characterization by several methods and encapsulation of the anticancer drug Paclitaxel (Taxol) within them, aiming for targeted delivery to cancerous sites and slow release at their vicinity. The KPs obtained were in micrometer in size. They are capable of encapsulating Taxol within them with a high encapsulation efficiency of 56% and a drug loading capacity of 2.360 g of Taxol per g keratin. As revealed by the SEM elemental analysis, KPs do not contain any toxic metal ion, and hence, they pose no toxicity to human cells. The pH-dependent release kinetics of the drug from KPs indicates that the drug is released faster when the pH of the solution is increased in the 5.0 to 7.0 pH range. The release kinetics obtained is impressive, and once targeted to the cancerous sites, using cancer directing agents, such as folic acid; a glutamate urea ligand known as DUPA; aminopeptidase N, also known as CD13; and FAP-α-targeting agents, the slow release of the drug is expected to destroy only the cancerous cells. The Noyes-Whitney dissolution model was used to analyze the release behavior of Taxol from KPs, which shows excellent fitting with experimental data. The pH dependence of drug release from keratin is also explained using the 3-D structures and keratin stability at different pH values. [ABSTRACT FROM AUTHOR]

Clostridioides difficile (C. difficile) is an opportunistic anaerobic bacterium that causes severe diseases of the digestive tract of humans and animals. One of the possible methods of preventing C. difficile infection is to develop a vaccine. The most promising candidates for vaccine antigens are the proteins involved in the adhesion phenomena. Among them, the FliC and FliD are considered to be suitable candidates. In this paper, the FliC and FliD protein polypeptide epitopes were mapped in silico and by using PEPSCAN procedure. We identified four promising epitopes: 117QRMRTLS123, 205MSKAG209 of FliC and 226NKVAS230, 306TTKKPKD312 of FliD protein. We showed that 117QRMRTLS123 sequence is not only located in TLR5-binding and activating region, as previously shown, but forms an epitope recognized by C. difficile-infected patients' antibodies. 205MSKAG209 is a C. difficile-unique, immunogenic sequence that forms an exposed epitope on the polymerized flagella structure which makes it a suitable vaccine antigen. 226NKVAS230 and 306TTKKPKD312 are well exposed and possess potential protective properties according to VaxiJen analysis. Our results open the possibility to use these epitopes as suitable anti-C. difficile vaccine antigens. [ABSTRACT FROM AUTHOR]

Lists articles to be published in the 'Immunology' periodical. Role of antigen presenting cells and interleukin-12 in the priming of antigen specific CD4[sup +] cells by immune stimulating complexes; Cell activation by monosaccharide lipid A analogs utilizing Toll-like receptor 4; Cytokine synthesis.

At present, no cure is available for COVID-19 but vaccines, antiviral drugs, immunoglobulins, or the combination of immunoglobulins with antiviral drugs have been suggested and are in clinical trials. The purpose of this paper is to discuss the role of a pharmacokinetic and viral load analysis as a basis for adjusting immunoglobulin dosing to treat COVID-19. We reviewed the pre-clinical and clinical literature that describes the impact of a high antigen load on pharmacokinetic data following antibody treatment. Representative examples are provided to illustrate the effect of high viral and tumor loads on antibody clearance. We then highlight the implications of these factors for facilitating the development and dosing of hyperimmune anti-SARS CoV2 immunoglobulin. Both nonclinical and clinical examples indicate that high antigen loads, whether they be viral, bacterial, or tumoral in origin, result in increased clearance and decreased area under the curve and half-life of antibodies. A dosing strategy that matches the antigen load can be achieved by giving initially high doses and adjusting the frequency of dosing intervals based on pharmacokinetic parameters. We suggest that study design and dose selection for immunoglobulin products for the treatment of COVID-19 require special considerations such as viral load, antibody-virus interaction, and dosing adjustment based on the pharmacokinetics of the antibody. [ABSTRACT FROM AUTHOR]

Introduction. Human ABO blood type antigens exhibit alternative phenotypes and genetically derived glycoconjugate structures that are located on the red cell surface which play an active role in the cells' physiology and pathology. Associations between the blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. However, due to lack of antigens of some blood groups, there have been some contentious issues with the association between the ABO blood group and vulnerability to certain infectious and noninfectious diseases. Objective. To review different literatures that show the association between ABO blood groups and different diseases. Method. Original, adequate, and recent articles on the same field were researched, and the researcher conducted a comprehensive review on this topic. Thus, taking out critical discussions, not only a descriptive summary of the topic but also contradictory ideas were fully retrieved and presented in a clear impression. In addition, some relevant scientific papers published in previous years were included. The article search was performed by matching the terms blood types/groups with a group of terms related to different diseases. The articles were screened and selected based on the title and abstract presented. Results. The susceptibility to various diseases, such as cancer, cardiovascular diseases, infections and hematologic disorders, cognitive disorders, circulatory diseases, metabolic diseases, and malaria, has been linked with ABO blood groups. Moreover, blood group AB individuals were found to be susceptible to an increased risk of cognitive impairment which was independent of geographic region, age, race, and gender. Disorders such as hypertension, obesity, dyslipidemia, cardiovascular disease (CVD), and diabetes were also more prevalent in individuals with cognitive impairment. Early etiological studies indicated that blood type O has a connection with increased incidence of cholera, plague, tuberculosis infections, and mumps, whereas blood type A is linked with increased incidence of smallpox and Pseudomonas aeruginosa infection; blood type B is also associated with increased incidence of gonorrhea, tuberculosis, and Streptococcus pneumoniae, E. coli, and salmonella infections; and blood type AB is associated with increased incidence of smallpox and E. coli and salmonella infections. Diabetes mellitus, hypercholesterolemia, arterial hypertension, and family history for ischemic heart disease are the most common risk factors for cardiovascular diseases and can be genetically transmitted to offspring. Higher incidence of cancers in the stomach, ovaries, salivary glands, cervix, uterus, and colon/rectum was common in blood type A people than in O type people. The link between the ABO blood type and thromboembolic diseases and bleeding risk are intervened by the glycosyltransferase activity and plasma levels and biologic activity of vWF (Von Willebrand factor), a carrier protein for coagulation factor VIII which is low in O type. Conclusion. Several studies related to the ABO phenotype show that genetically determined human ABO blood groups were correspondingly linked with an increased risk of various infectious and noninfectious diseases. However, further investigations are needed particularly on the molecular level of ABO blood groups and their association with various diseases. [ABSTRACT FROM AUTHOR]

This paper provides a summary of mass COVID-19 testing of almost the entire population in Slovakia by antigen tests. We focused on the results delivered by two testing rounds and analyzed the benefits and weaknesses of such type of testing. We prepared mathematical models to critically examine the effectiveness of the testing, and we also estimated the number of potentially sick people that would become infected by those marked as positives by antigen tests. Our calculations have proven that antigen testing in hotspots can flatten the curve of daily newly reported cases significantly, but in regions with low-risk of COVID-19, the benefit of such testing is questionable. As for the regions with low infection rates, we could only estimate the proportion of true and false-positive cases because the national health authority had not validated the results by RT-PCR tests. Therefore, this work can serve as an introductory study on the first nationwide testing by antigen tests in Europe. [ABSTRACT FROM AUTHOR]

This paper presents a study of the response of FRET based DNA aptasensors in the intracellular environment. Herein, we extend previous studies of aptasensors functioning in the extracellular environment to detection of antigens in the intracellular environment. An essential step in this research is the use of a novel means of achieving the endocytosis of aptasensors. Specifically, it is demonstrated that functioning aptasensors are successfully endocytosed by functionalizing the aptasensors with endocytosis—inducing DSS peptides. [ABSTRACT FROM AUTHOR]

Purpose: Toxoplasma gondii is an opportunistic parasite infecting all warm-blooded animals including humans. The dense granule antigens (GRAs) play an important role in parasite survival and virulence and in forming the parasitophorous vacuole. Identification of protein characteristics increases our knowledge about them and leads to develop the vaccine and diagnostic studies. Materials and Methods: This paper gave a comprehensive definition of the important aspects of GRA12 protein, including physico-chemical features, a transmembrane domain, subcellular position, secondary and tertiary structure, potential epitopes of B-cells and T-cells, and other important features of this protein using different and reliable bioinformatics methods to determine potential epitopes for designing of a high-efficient vaccine. Results: The findings showed that GRA12 protein had 53 potential post-translational modification sites. Also, only one transmembrane domain was recognized for this protein. The secondary structure of GRA12 protein comprises 35.55% alpha-helix, 19.50% extended strand, and 44.95% random coil. Moreover, several potential B- and T-cell epitopes were identified for GRA12. Based on the results of the Ramachandran plot, 79.26% of amino acid residues were located in favored, 11.85% in allowed and 8.89% in outlier regions. Furthermore, the results of the antigenicity and allergenicity assessment noted that GRA12 is immunogenic and non-allergenic. Conclusion: This research provided important basic and conceptual data on GRA12 to develop an effective vaccine against acute and chronic toxoplasmosis for further in vivo investigations. More studies are required on vaccine development using the GRA12 alone or combined with other antigens in the future. [ABSTRACT FROM AUTHOR]

Microscopy is the gold standard for malaria epidemiology, but laboratory and point-of-care (POC) tests detecting parasite antigen, DNA, and human antibodies against malaria have expanded this capacity. The island nation of Haiti is endemic for Plasmodium falciparum (Pf) malaria, though at a low national prevalence and heterogenous geospatial distribution. In 2015 and 2016, serosurveys were performed of children (ages 6–7 years) sampled in schools in Saut d'Eau commune (n = 1,230) and Grand Anse department (n = 1,664) of Haiti. Children received malaria antigen rapid diagnostic test and provided a filter paper blood sample for further laboratory analysis of the Pf histidine-rich protein 2 (HRP2) antigen, Pf DNA, and anti-Pf IgG antibodies. Prevalence of Pf infection ranged from 0.0–16.7% in 53 Saut d'Eau schools, and 0.0–23.8% in 56 Grand Anse schools. Anti-Pf antibody carriage exceeded 80% of students in some schools from both study sites. Geospatial prediction ellipses were created to indicate clustering of positive tests within the survey areas and overlay of all prediction ellipses for the different types of data revealed regions with high likelihood of active and ongoing Pf malaria transmission. The geospatial utilization of different types of Pf data can provide high confidence for spatial epidemiology of the parasite. [ABSTRACT FROM AUTHOR]

Local allergic rhinitis (LAR) is a specific phenotype of allergic rhinitis. One characteristic feature of LAR is a medical history indicative of an allergic disease, negative skin-prick test results, undetectable levels of specific IgE, and a positive allergen-specific nasal provocation test. This paper presents a case of a patient with LAR and underlying house dust mite allergy, who was ultimately diagnosed >10 years after the onset of his first symptoms. Currently, there are only pharmacological treatments available for LAR. However, some studies show encouraging results with the use of allergen-specific immunotherapy in LAR, which offer hope for a future use of this causative treatment in LAR patients. Int J Occup Med Environ Health. 2020;33(2):241-6. [ABSTRACT FROM AUTHOR]

The body's autoimmune process is involved in the development of Graves' disease (GD), which is manifested by an overactive thyroid gland. In some patients, autoreactive inflammatory reactions contribute to the development of symptoms such as thyroid ophthalmopathy, and the subsequent signs and symptoms are derived from the expansion of orbital adipose tissue and edema of extraocular muscles within the orbit. The autoimmune process, production of antibodies against self-antigens such as TSH receptor (TSHR) and IGF-1 receptor (IGF-1R), inflammatory infiltration, and accumulation of glycosaminoglycans (GAG) lead to edematous-infiltrative changes in periocular tissues. As a consequence, edema exophthalmos develops. Orbital fibroblasts seem to play a crucial role in orbital inflammation, tissue expansion, remodeling, and fibrosis because of their proliferative activity as well as their capacity to differentiate into adipocytes and myofibroblasts and production of GAG. In this paper, based on the available medical literature, the immunological mechanism of GO pathogenesis has been summarized. Particular attention was paid to the role of orbital fibroblasts and putative autoantigens. A deeper understanding of the pathomechanism of the disease and the involvement of immunological processes may give rise to the introduction of new, effective, and safe methods of treatment or monitoring of the disease activity. [ABSTRACT FROM AUTHOR]