Search

Veterinary drug residues in food-producing animals pose a threat to human health and public safety, and accurate measurement of these drug residues is necessary. However, detecting nitrofuran metabolite residues is challenging because of their low molecular weight and the long derivatisation time required for their indirect detection. Current antibodies produced against these metabolites have limited accuracy and sensitivity owing to the traditional and ineffective hapten design based on the reaction of 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ) with nitrobenzaldehyde. In this study, a new antigen strategy was adopted using an original-structure-based hapten design combined with a new carrier protein with immunosynergistic effects to produce a monoclonal antibody that could recognise the metabolite of furaltadone (AMOZ) directly without derivatisation with excellent analytical performance. Finally, a gold-based paper lateral flow immunoassay for AMOZ without derivatisation was established with a visual limit of detection of 5 ng/mL, IC 50 of 0.97 ng/mL and linear range (IC 20 ∼IC 80) of 0.45–2.07 ng/mL. The method was sensitive and accurate, and detection was completed within 10 min. This new antigen design strategy provides a theoretical basis and reference for antibody production of other ultrasmall molecules. [Display omitted] • An antigen strategy of AMOZ was proposed by hapten design and new carrier proteins. • The excellent antibody directly recognizes AMOZ without derivatization. • Effect of EP distribution and spatial structure to antibody production was studied. • This method could be used as a rapid screening method for AMOZ analysis on site. [ABSTRACT FROM AUTHOR]

In this study, we describe the design and successful synthesis of a new hapten, which we used to prepare an anti-zilpaterol mouse monoclonal antibody (mAb) with an IC50 of 0.31 ng mL−1 and a limit of detection (LOD) of 0.02 ng mL−1. A colloidal gold immunochromatographic test strip was further developed and optimized using the antibody, and cross-reactivity experiments were carried out to prove its good specificity. Semi-quantitative and quantitative detections of zilpaterol were evaluated in swine urine and pork samples using the test strips. For semi-quantitative detection in swine urine and pork samples, the visual limit of detection values were 0.5 μg kg−1 and 0.5 μg kg−1, and the cut-off values were 5 μg kg−1 and 5 μg kg−1, respectively. For quantitative detection, the calculated limit of detection values were 0.08 μg kg−1 and 0.12 μg kg−1, and the remaining values were 10 μg kg−1 and 10 μg kg−1. The developed gold nanoparticle-based immunochromatographic assay is highly suitable for on-site detection and rapid preliminary screening of zilpaterol in swine urine and pork samples. [ABSTRACT FROM AUTHOR]

Furthermore, it has been reported that MS patients using anti-CD20 therapy have suppressed antibody response to infection with the novel coronavirus (SARS-CoV-2) and to some vaccines (not against COVID-19) [[1], [3]-[5]]. Dear Sirs, We read with great interest the paper by Khayat Khoei et al. which presented negative anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) antibody response after Pfizer SARS-CoV-2 vaccination in a patient with relapsing-remitting multiple sclerosis (RRMS) on ocrelizumab [[1]]. [Extracted from the article]

• An immunosensor was developed for the determination of amanitins. • Half-maximal inhibitory concentration was 0.48 ng/mL and the LOD was 0.095 ng/mL. • Good correlations of the results verified by immunosensor and LC–MS/MS. Amanitin (AMA) is responsible for human fatalities after ingestion of poisonous mushrooms, thus, a rapid and accurate detection method is urgently needed. Here, gold nanoparticle-based immunosensor with monoclonal antibody against AMA was constructed for rapid detection of alpha- and beta-amanitin (α- and β-AMA) in mushroom, serum and urine samples. Under optimized conditions, the visual limits of detection (vLOD) and calculated LOD for α-AMA and β-AMA in mushroom were 10 ng/g, 20 ng/g, and 0.1 ng/g, 0.2 ng/g, respectively. Analysis of wild mushroom samples was also performed using a strip scan reader in the 10 min range. Furthermore, in mushrooms containing amatoxins results were confirmed and compared with those determined by liquid chromatography tandem mass spectrometry. Thus, this immunosensor provided a useful monitoring tool for rapid detection and screening of mushroom samples and in serum and urine from subjects who accidentally consumed AMA-containing mushrooms. [ABSTRACT FROM AUTHOR]

Introduction: Studies indicate that individuals with chronic conditions and specific baseline characteristics may not mount a robust humoral antibody response to SARS-CoV-2 vaccines. In this paper, we used data from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a longitudinal state-wide seroprevalence program that has enrolled more than 90,000 participants, to evaluate the role of chronic diseases as the potential risk factors of non-response to SARS-CoV-2 vaccines in a large epidemiologic cohort. Methods: A participant needed to complete an online survey and a blood draw to test for SARS-CoV-2 circulating plasma antibodies at four-time points spaced at least three months apart. Chronic disease predictors of vaccine non-response are evaluated using logistic regression with non-response as the outcome and each chronic disease + age as the predictors. Results: As of April 24, 2023, 18,240 participants met the inclusion criteria; 0.58% (N = 105) of these are non-responders. Adjusting for age, our results show that participants with self-reported immunocompromised status, kidney disease, cancer, and "other" non-specified comorbidity were 15.43, 5.11, 2.59, and 3.13 times more likely to fail to mount a complete response to a vaccine, respectively. Furthermore, having two or more chronic diseases doubled the prevalence of non-response. Conclusion: Consistent with smaller targeted studies, a large epidemiologic cohort bears the same conclusion and demonstrates immunocompromised, cancer, kidney disease, and the number of diseases are associated with vaccine non-response. This study suggests that those individuals, with chronic diseases with the potential to affect their immune system response, may need increased doses or repeated doses of COVID-19 vaccines to develop a protective antibody level. [ABSTRACT FROM AUTHOR]

This paper develops a mathematical model to investigate the Human Immunodeficiency Virus (HIV) infection dynamics. The model includes two transmission modes (cell-to-cell and cell-free), two adaptive immune responses (cytotoxic T-lymphocyte (CTL) and antibody), a saturated CTL immune response, and latent HIV infection. The existence and local stability of equilibria are fully characterized by four reproduction numbers. Through sensitivity analyses, we assess the partial rank correlation coefficients of these reproduction numbers and identify that the infection rate via cell-to-cell transmission, the number of new viruses produced by each infected cell during its life cycle, the clearance rate of free virions, and immune parameters have the greatest impact on the reproduction numbers. Additionally, we compare the effects of immune stimulation and cell-to-cell spread on the model's dynamics. The findings highlight the significance of adaptive immune responses in increasing the population of uninfected cells and reducing the numbers of latent cells, infected cells, and viruses. Furthermore, cell-to-cell transmission is identified as a facilitator of HIV transmission. The analytical and numerical results presented in this study contribute to a better understanding of HIV dynamics and can potentially aid in improving HIV management strategies. [ABSTRACT FROM AUTHOR]

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses. [ABSTRACT FROM AUTHOR]

This paper summarizes key features of the dose‐finding strategies used in the development of 11 approved new molecular entities that are first‐in‐class enzyme replacement therapy (ERT), with a goal to gain insight into the dose exploration approaches to inform efficient dose‐finding in future development of biological products for Inborn Errors of Metabolism (IEM). Dose exploration should preferably begin in in vitro studies, followed by testing multiple doses in an appropriate animal disease model, when available, which can provide important information for dose assessment in humans. Performing adequate dose‐finding in early phase clinical studies in a well‐defined study population, including pediatric subjects, is generally critical to inform dose selection for pivotal trials; alternatively, additional dose exploration can be incorporated as part of a pivotal trial. Two important considerations for successful dose selection include (1) identifying appropriate disease‐specific endpoints, including pharmacodynamic (PD) end points and intermediate clinical end points or clinical end points, and (2) designing a study with adequate treatment durations for evaluating these end points. Appropriately selected PD biomarkers is useful for dose selection, and early development of these biomarkers can facilitate the overall clinical development program. Optimization of ERT doses, as well as evaluations of patient intrinsic factors and/or immune tolerance strategies may be necessary to overcome antibody responses or increase efficacy in IEM. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs), crucial in medicine and biopharmaceuticals, require optimized large-scale production to meet high clinical dosage demands. Most of the processes for industrial mAb production rely on fed-batch operations, resulting in significant downtime. Transitioning to fully continuous and integrated processes holds the potential to boost product yield, enhance quality, and reduce storage costs for intermediate products. The integrated continuous mAb production process can be divided into the upstream and downstream processes. One crucial aspect that ensures the continuity of the integrated process is the switching of the capture columns, which are typically chromatography columns operated in a fed-batch manner downstream. Due to the discrete nature of the switching operation, advanced process control algorithms such as economic MPC (EMPC) are computationally difficult to implement. This is because an integer nonlinear program (INLP) needs to be solved online at each sampling time. This paper introduces two computationally-efficient approaches for EMPC implementation, namely, a sigmoid function approximation approach and a rectified linear unit (ReLU) approximation approach. It also explores the application of deep reinforcement learning (DRL). These three methods are compared to the traditional switching approach which is based on a 1 % product breakthrough rule and which involves no optimization. • An optimal control formulation for the switching operation in mAb production. • Two approximation methods for solving the optimal control problem. • Extensive simulation results showing the properties of the solving methods. [ABSTRACT FROM AUTHOR]

This paper is concerned with the existence and nonexistence of traveling waves of a virus infection model with humoral immunity, cell‐to‐cell transmission, and general nonlinear incidence. Our results show that the existence of traveling wave solutions is determined not only by the basic reproduction number R0$$ {\mathcal{R}}_0 $$ of virus infection and the antibody response reproduction number R1$$ {\mathcal{R}}_1 $$ but also by the critical wave speed c∗$$ {c}^{\ast } $$. More precisely, we obtain the existence of traveling wave solution connecting infection‐free equilibrium and antibody‐free infection equilibrium for R0>1,R1<1$$ {\mathcal{R}}_0>1,{\mathcal{R}}_1<1 $$, and c>c∗$$ c>{c}^{\ast } $$ and connecting infection‐free equilibrium and antibody‐present infection equilibrium for R0>1,R1>1$$ {\mathcal{R}}_0>1,{\mathcal{R}}_1>1 $$, and c>c∗$$ c>{c}^{\ast } $$. The existence of traveling wave solution connecting infection‐free equilibrium and antibody‐present infection equilibrium is discussed. Some numerical simulations are carried out to illustrate our analytical results. [ABSTRACT FROM AUTHOR]

This paper presents two viral infection models that describe dynamics of the virus under the effect of two distinct types of antibodies. The first model considers the population of five compartments, target cells, infected cells, free virus particles, antibodies type-1 and antibodies type-2. The presence of two types of antibodies can be a result of secondary viral infection. In the second model, we incorporate the latently infected cells. We assume that the antibody responsiveness is given by a combination of the self-regulating antibody response and the predator–prey-like antibody response. For both models, we verify the nonnegativity and boundedness of their solutions, then we outline all possible equilibria and prove the global stability by constructing proper Lyapunov functions. The stability of the uninfected equilibrium EQ 0 and infected equilibrium EQ * is determined by the basic reproduction number R 0 . The theoretical findings are verified through numerical simulations. According to the outcomes, the trajectories of the solutions approach EQ 0 and EQ * when R 0 ≤ 1 and R 0 > 1 , respectively. We study the sensitivity analysis to show how the values of all the parameters of the suggested model affect R 0 under the given data. The impact of including the self-regulating antibody response and latently infected cells in the viral infection model is discussed. We showed that the presence of the self-regulating antibody response reduces R 0 and makes the system more stabilizable around EQ 0 . Moreover, we established that neglecting the latently infected cells in the viral infection modeling leads to the design of an overflow of antiviral drug therapy. [ABSTRACT FROM AUTHOR]

Individuals with a history of coronavirus disease 2019 (COVID-19) exhibit memory immunity acquired during natural infection. However, a decline in immunity after infection renders these individuals vulnerable to re-infection, in addition to a higher risk of infection with new variants. This systematic review examined related studies to elucidate the antibody response in these infected individuals after messenger ribonucleic acid (mRNA) vaccination. Hence, the focus of this review was to ascertain differences in the concentration of binding and neutralising antibodies of previously infected individuals in comparison to those of infection-naïve individuals after administration of two doses of mRNA vaccination through available case-control and cohort studies. Positive reverse transcriptase-polymerase chain reaction (RT-PCR) test or detectable anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at the baseline in included studies showed categorisation of infected and uninfected individuals. This review utilised three online databases: PubMed, Scopus and Cochrane with the following keywords: (COVID-19 OR 'Coronavirus Disease 2019' OR SARS-CoV-2) AND Immun* AND (Pfizer OR BioNTech OR BNT162b2 OR Comirnaty OR Moderna OR mRNA-1273) from January 2019 to July 2021. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) 2020 guidelines and assessment based on the Crowe Critical Appraisal Tool (CCAT), we included 13 related qualified papers of observational studies discerning the binding and neutralising antibody concentrations of infected and uninfected individuals after administration of mRNA vaccines, such as the BNT162b2 and mRNA-1273 vaccine. The mRNA vaccines induced robust binding and neutralising antibody responses in both groups. However, infected individuals showed induction of higher antibody responses in a shorter time compared to uninfected individuals. Hence, a single dose of mRNA vaccination for infected individuals may be sufficient to reach the same level of antibody concentration as that observed in uninfected individuals after receiving two doses of vaccination. [ABSTRACT FROM AUTHOR]

Within-host models describe the dynamics of immune cells when encountering a pathogen, and how these dynamics can lead to an individual-specific immune response. This systematic review aims to summarize which within-host methodology has been used to study and quantify antibody kinetics after infection or vaccination. In particular, we focus on data-driven and theory-driven mechanistic models. PubMed and Web of Science databases were used to identify eligible papers published until May 2022. Eligible publications included those studying mathematical models that measure antibody kinetics as the primary outcome (ranging from phenomenological to mechanistic models). We identified 78 eligible publications, of which 8 relied on an Ordinary Differential Equations (ODEs)-based modelling approach to describe antibody kinetics after vaccination, and 12 studies used such models in the context of humoral immunity induced by natural infection. Mechanistic modeling studies were summarized in terms of type of study, sample size, measurements collected, antibody half-life, compartments and parameters included, inferential or analytical method, and model selection. Despite the importance of investigating antibody kinetics and underlying mechanisms of (waning of) the humoral immunity, few publications explicitly account for this in a mathematical model. In particular, most research focuses on phenomenological rather than mechanistic models. The limited information on the age groups or other risk factors that might impact antibody kinetics, as well as a lack of experimental or observational data remain important concerns regarding the interpretation of mathematical modeling results. We reviewed the similarities between the kinetics following vaccination and infection, emphasising that it may be worth translating some features from one setting to another. However, we also stress that some biological mechanisms need to be distinguished. We found that data-driven mechanistic models tend to be more simplistic, and theory-driven approaches lack representative data to validate model results. [ABSTRACT FROM AUTHOR]

In the presence of uncertainty, the optimum obtained based on a nominal identified model can neither provide any performance guarantee nor ensure that critical constraints are satisfied, which is crucial for e.g., bioprocess applications characterized by a high degree of complexity combined with costly experiments. Hence, uncertainty should be considered in the optimization and, furthermore, experiments designed to reduce the uncertainty most important for optimization. Herein, we propose a general framework that combines model-based robust optimization with optimal experiment design. The proposed framework can take advantage of prior knowledge in the form of a mechanistic model structure, and the importance of this is demonstrated by comparing it to more standard black-box models typically employed in learning. Through optimal experiment design, we repeatedly reduce the uncertainty most relevant for optimization so as to maximize the potential for improving the worst-case performance by balancing between exploration and exploitation. This makes the proposed method an efficient model-based robust optimization framework, especially in cases with limited experimental resources. The main part of the paper focuses on the case with modeling uncertainty that can be reduced with the availability of more experimental data. Towards the end of the paper, we consider extending the method to also include inherent uncertainty, such as input uncertainty and unmeasured disturbances. The effectiveness of the method is illustrated through a realistic simulation case study of medium optimization of Chinese hamster ovary cell cultivation in continuous monoclonal antibody production, where the metabolic network consists of 23 extracellular metabolites and 126 reactions. [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]

In 1940, Linus Pauling proposed his template theory of antibody formation, one of many such theories that rejected Paul Ehrlich's selective theory of preformed "receptors" (antibodies), assuming instead a direct molding of antibody shapes onto that of the antigen. Pauling believed that protein shapes--independently of amino acid sequences--determined antibody specificity and biological specificity in general. His theory was informed by his pioneering work on protein structure, and it was inspired by the intuitive "rule of parsimony" and simplicity. In 1942, Pauling published his alleged success in producing specific artificial antibodies through experiments based on his 1940 theory. However, his experiments could not be reproduced by prominent immunochemists at the time, and, later, it became generally accepted that antibody specificity was not generated according to Pauling's and others' "instruction" template theories. A citation analysis shows that Pauling's papers on antibody generation continue to be cited as, among other things, pioneering studies of a chemical technology called "molecular imprinting." The examples of Pauling and other protein chemists are used in this paper to demonstrate that scientific belief, philosophical concepts, and subjective theory preferences facilitated the occurrence of irreproducibility in immunochemistry and beyond. The article points to long-term consequences for the scientific community if irreproducible results are not acknowledged. It concludes by arguing that despite the risks, e.g., for the occurrence and perpetuation of irreproducible results that they entail, subjectivity and a commitment to scientific convictions have often been pre-requisites for the generation, and holding on to, scientific innovation in the face of doubt and rejection from the scientific community. [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]

Sablefish (Anoplopoma fimbria) are an emerging aquaculture species native to the continental shelf of the northern Pacific Ocean. There is limited information on both innate and adaptive immunity for this species and new tools are needed to determine antibody response following vaccination or disease outbreaks. In this paper, a monoclonal antibody, UI-25A, specific to sablefish IgM was produced in mice. Western blotting confirmed UI-25A recognizes the heavy chain of IgM and does not cross react to proteins or carbohydrates in serum of four other teleost species. An ELISA was developed to measure Aeromonas salmonicida specific IgM in the plasma of sablefish from a previous experiment where fish were immunized with a proprietary A. salmonicida vaccine. UI-25A was used in Western blot analyses to identify immunogenic regions of A. salmonicida recognized by this specific IgM from vaccinated sablefish. Immunofluorescent staining also demonstrated the ability of UI-25A to recognize membrane-bound IgM and identify IgM + cells in the head kidney. These results demonstrate the usefulness of UI-25A as a tool to improve the understanding of antibody-mediated immunity in sablefish as well as to provide valuable information for vaccine development and expansion of aquaculture efforts for this fish species. • A mAb, UI-25A, specific to the heavy chain of sablefish IgM is produced. • The mAb detects differences in A. salmonicida antibody titers after vaccination. • The mAb detects immunogenic regions of A. salmonicida via western blotting. • The UI-25A mAb also detects IgM + cells using immunofluorescent microscopy. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) have emerged as the dominant class of therapeutic moieties due to their superior therapeutic potential and safety profile. Downstream processing plays a pivotal role in ensuring the purity, yield, and quality of these therapeutic products. The biopharmaceutical industry generates a significant amount of data, making it an attractive target for creating machine learning (ML) and deep learning (DL) applications. This paper reports a DL-based 2D-convolutional neural network (2D-CNN) to predict: (i) Protein A mAb elute concentration, (ii) Cation exchange (CEX) mAb elute concentration, (iii) % Acidic variant, (iv) Aggregate (%), and (v) % Basic variant from process data that is routinely collected during biopharma manufacturing, including Protein A elution UV, CEX elution UV, CEX elution conductivity, and post viral inactivation pH profiles. Further, interpretation of predicted outputs using the SHAPLEY technique and optimization through multi-objective Bayesian optimization methods have been attempted so as to match the biosimilar to the reference molecule with respect to the critical quality attributes. It is observed that the proposed model outperforms other published approaches in prediction. The optimum results were experimentally validated by performing three consecutive runs, and a mean percentage deviation of less than 3 % was reported. The proposed approach demonstrates the feasibility of real-time prediction and optimization in biopharmaceutical product manufacturing using CNN-aided modeling and multi-objective weighted sum optimization. [Display omitted] • A data-driven 2D CNN model is implemented for prediction of output variables. • SHAPLEY technique is employed for model interpretation. • Bayesian optimization is utilized for attaining optimum target variables. • Experimental verification of optimum output is performed with three runs. [ABSTRACT FROM AUTHOR]

This review article concerns the production of recombinant antibody fragments for applications mainly in the diagnostic sector. The so-called "point of care diagnostics" is very important for timely diagnosis and treatment, thus being able to save lives and resources. There is intense pressure for more accurate and less expensive rapid diagnostic tests, with a value preferably <$1. Thus, the large-scale cost-effective production of recombinant antibodies is vital. The importance of Escherichia coli toward the production of inexpensive rapid tests will be explained in this review paper. Details about the different strains of E. coli, the strategies used for the insertion and the expression of recombinant proteins, and the challenges that still exist are provided. Afterward, the importance of the expression scale and culture parameters in the final yield of the antibodies are examined. From this analysis, it appears that for good yields of recombinant antibodies, aside from appropriate gene transfer and expression, the culturing parameters are of paramount importance. Larger scale production is more favorable, mainly due to the higher cell densities that can be achieved. Yields of functional Fab fragments in the range of 10–20 mg/L are considered good in shake flasks, whereas in bioreactors can be up to 1–2 g/L. An amount of 10–500 mg of such antibody per million rapid tests is required. Despite the substantial importance of the production of the antibodies and their fragments, their downstream processing should be appropriately considered from the beginning for achieving the target value of the final rapid diagnostic tests. [ABSTRACT FROM AUTHOR]

Serological databases represent an important source of information to perceive COVID-19 impact on health professionals involved in combating the disease. This paper describes SerumCovid, a COVID-19 serological database focused on the diagnosis of health professionals, providing a preliminary analysis to contribute to the understanding of the antibody response to the SARS-CoV-2. The study population comprises 321 samples from 236 healthcare and frontline workers fighting COVID-19 in Vitória de Santo Antão, Brazil. Samples were collected from at least six days of symptoms to more than 100 days. The used immunoenzymatic assays were Euroimmun Anti-SARS-CoV-2 ELISA IgG and IgA. The most common gender in SerumCovid is female, while the most common age group is between 30 and 39 years old. However, no statistical differences were observed in either genders or age categories. The most reported symptoms were fatigue, headaches, and myalgia. Still, some subjects presented positive results for IgA after 130 days. Based on a temporal analysis, we have not identified general patterns as subjects presented high and low values of IgA and IgG with different evolution trends. Unexpectedly, for subjects with both serological tests, the outcome of IgA and IgG tests were the same (either positive or negative) for more than 80% of the samples. Therefore, SerumCovid helps better understand how COVID-19 affected healthcare and frontline workers, which increases knowledge about the infection and enables direct prevention actions. [ABSTRACT FROM AUTHOR]

Understanding the T-cell response to SARS-CoV-2 is key in patients who lack antibody production. We demonstrate the applicability of a functional assay to measure the T-cell response in a cohort of patients with immunodeficiency. T-cell responses to COVID are now linked to improved outcomes. This paper demonstrates a method to robustly test responses for routine diagnostic use in healthy controls and those unable to make a detectable antibody response due to underlying immune deficiency (primary or acquired). [ABSTRACT FROM AUTHOR]

The emergence of the covid19 pandemic has forced many countries to be more focused on the technologies that can save human life. A lot of efforts have focused on containment and mitigation actions with varying degrees of success. However, lack of attention given to administering urgent requests for convalescent plasma blood as part of treatment for critical covid19 patients although the passive administration of antibodies from a person who has convalesced may be an effective therapy for those patients who have yet to develop their antibody response. Hence, interest in the use of convalescent plasma has been rising, not only commenced by medical professionals but also among patients' family members, especially for urgent requests. This paper proposed timelinebased posts to tackle the urgent-request issue that sort based on first come first serve priority. From this timeline, the people in search of donors may find donors' information and location quickly. Furthermore, we added a timeline page, search function, a virtual assistant (chatbot) that automatically shares posts to social media without exiting the app, etc. These features promote the hit to the right users and their respond faster than before. The previous study reported from the 40 PSARS patients undergoing ribavirin and methylprednisolone treatment, 19 were administered with convalescent plasma, whereas 21 were given an additional dose of methylprednisolone. The group of patients who were treated with plasma therapy showed better recovery and reduced mortality. With this situation, we hope our contribution in the form of an Android app can assist those in need at the right time and save more lives. Moreover, this app can be referred to as a model for other comparable apps. [ABSTRACT FROM AUTHOR]

Nickel (Ni) in ambient air may vary regionally with contributions from both natural processes and anthropogenic activities. Exposure to Ni compounds in ambient air above a certain level is associated with acute adverse effects, such as upper respiratory tract irritation, pneumonitis, and chronic adverse effects, such as respiratory cancer. Inhalation reference exposure standards are enacted in different jurisdictions to minimize exposures to ambient Ni above levels that can elicit adverse effects. This paper reports a guideline-/GLP-compliant study designed for setting inhalation exposure standards to protect from immunological effects associated with acute exposure to Ni. Female CD-1 mice were exposed via whole-body inhalation to aerosolized nickel chloride hexahydrate for 24-hr at nominal (vs. mean analyzed) concentrations of 20 (16), 50 (44) and 100 (81) µg Ni/m3. Host T-cell antibody immunological responses to intravenously-injected sheep red blood cells were then measured ex vivo in an Antibody-Forming Cell (AFC) assay. Exposure to the Ni substance significantly decreased spleen cell levels by 33%, but this was within biological variability for outbred mice. No concurrent decreases in spleen, thymus, or body weights were noted. No immunosuppression was observed with the Ni substance in the context of Total Spleen Activity [IgM AFC/spleen (× 103)] and Specific Activity [IgM AFC/spleen cells (× 106)]. Significant concentration-independent increases in Total Spleen Activity and Specific Activity seen with the nickel chloride hexahydrate were normal and within biological variability for outbred mice. In contrast, cyclophosphamide (positive control) significantly decreased spleen cell numbers, spleen and thymus weights, and abolished Specific Activity and Total Spleen Activity. Based on results here, an NOAEC of 81 µg Ni/m3 for immunosuppressive effects from inhaled nickel chloride hexahydrate was identified. It is hoped this value can be used to derive a reference standard for human exposure to ambient Ni. [ABSTRACT FROM AUTHOR]

• RSV neutralization assays are complex biological assays used for measurement of functional antibody responses. • A broad variety of RSV neutralization assay formats are currently in use. • Use of the 1st International Standard for Antiserum to RSV is necessary to harmonize neutralization assay output across formats. • This paper outlines good practices for key assay components and data analysis to promote the quality and consistency of RSV neutralization assay results. Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among children and infants worldwide, yet no licensed vaccine exists to reduce the risk of disease. At least 16 RSV vaccine candidates are currently in clinical development and many are designed to induce robust virus neutralizing immune responses. RSV neutralizing antibody (nAb)-mediated interventions such as intravenous immunoglobulin (IVIG) and palivizumab provide passive protection against serious lower respiratory tract disease due to RSV, validating nAbs as a correlate of protection. To identify correlates of protection for vaccine candidates that have demonstrated their protective efficacy, an investigator can use assays designed to measure nAb responses. However, there is no standard method of measurement; individual laboratories have developed their own methods to measure the ability of nAbs to reduce the infectivity of a defined virus dose in a variety of cell lines, leading to establishment of the broad variety of RSV neutralization assay formats currently in use. Standardizing the RSV neutralization assay is an essential step toward better assessment of nAb responses to vaccine candidates. Use of a common reference standard by all makes comparing the immunogenicity of different vaccine candidates feasible. In the context of vaccine development, the WHO 1st International Standard for Antiserum to RSV (RSV IS) has been shown to be suitable for harmonizing results across laboratories and assay formats used to measure nAb titers to RSV/A and RSV/B in human sera. This review describes the broad variety of RSV virus neutralization assay formats currently in use and the importance of the RSV IS for harmonization of results across formats and across laboratories. It also outlines good practices for key assay components and data analysis to promote the quality and consistency of measuring RSV nAb titers in serum specimens. [ABSTRACT FROM AUTHOR]

Psychological and behavioural may enhance vaccine effectiveness. We conducted a systematic review and network meta-analysis (NMA) to examine the effects of non-pharmacological adjuvants on vaccine effectiveness, as measured by antibody responses to vaccination. Electronic databases (EMBASE, Medline, PsychINFO, CINAHL) were searched from inception to 6th February 2018. This yielded 100 eligible papers, reporting 106 trials: 79 interventions associated with diet and/or nutrition; 12 physical activity interventions and 9 psychological interventions.Over half (58/106) of trials reported evidence of an enhanced antibody response to vaccination across one or more outcomes. The NMA considered the comparative effects between all intervention types, control and placebo for antibody titres (48 studies), seroconversion (25 studies) and seroprotection (23 studies) separately. The NMA provided weak evidence in support of nutritional formulae and probiotics in increasing antibody titres. This review offers a comprehensive summary of the literature on non-pharmacological interventions as vaccine adjuvants. The evidence is characterised by considerable heterogeneity but provides early evidence in support of nutritional formulae and probiotic interventions. Psychological and exercise-based interventions were characterised by limited and unreliable evidence. Large, well-designed studies including consistent core outcomes and measures of intervention adherence and fidelity are required. [ABSTRACT FROM AUTHOR]

Biopharmaceuticals are used to treat a range of diseases from arthritis to cancer, however, since the advent of these highly specific, effective drugs, there have been challenges involved in their production. The most common biopharmaceuticals, monoclonal antibodies (mAbs), are vulnerable to aggregation and precipitation during processing. Freeze thaw cycles (FTCs), which can be required for storage and transportation, can lead to a substantial loss of product, and contributes to the high cost of antibody production. It is therefore necessary to monitor aggregation levels at susceptible points in the production pathway, such as during purification and transportation, thus contributing to a fuller understanding of mAb aggregation and providing a basis for rational optimisation of the production process. This paper uses attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and spectroscopic imaging to investigate the effect of these potentially detrimental FTCs on protein secondary structure in both static wells and under flowing conditions, using lysozyme as a model protein. The results revealed that the amount of protein close to the surface of the ATR crystal, and hence level of aggregates, increased with increasing FTCs. This was observed both within wells and under flow conditions, using conventional ATR-FTIR spectroscopy and ATR-FTIR spectroscopic imaging. Interestingly, we also observed changes in the Amide I band shape indicating an increase in β-sheet contribution, and therefore an increase in aggregates, with increasing number of FTCs. These results show for the first time how ATR-FTIR spectroscopy can be successfully applied to study the effect of FTC cycles on protein samples. This could have numerous broader applications, such as in biopharmaceutical production and rapid diagnostic testing. [ABSTRACT FROM AUTHOR]

In this study, a key issue to be addressed is the safe disposal of hybridoma instability. Hybridoma technology was used to produce anti–O. viverrini monoclonal antibody. Previous studies have shown that antibody production via antibody phage display can sustain the hybridoma technique. This paper presents the utility of antibody phage display technology for producing the phage displayed KKU505 Fab fragment and using experiments in concomitant with molecular simulation for characterization. The phage displayed KKU505 Fab fragment and characterization were successfully carried out. The KKU505 hybridoma cell line producing anti–O. viverrini antibody predicted to bind to myosin was used to synthesize cDNA so as to amplify the heavy chain and the light chain sequences. The KKU505 displayed phage was constructed and characterized by a molecular modeling in which the KKU505 Fab fragment and -O. viverrini myosin head were docked computationally and it is assumed that the Fab fragment was specific to -O. viverrini on the basis of mass spectrometry and Western blot. This complex interaction was confirmed by molecular simulation. Furthermore, the KKU505 displayed phage was validated using indirect enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry. It is worthy to note that ELISA and immunohistochemistry results confirmed that the Fab fragment was specific to the -O. viverrini antigen. Results indicated that the approach presented herein can generate anti–O. viverrini antibody via the phage display technology. This study integrates the use of phage display technology together with molecular simulation for further development of monoclonal antibody production. Furthermore, the presented work has profound implications for antibody production, particularly by solving the problem of hybridoma stability issues. [ABSTRACT FROM AUTHOR]

The fast and untraceable virus mutations take lives of thousands of people before the immune system can produce the inhibitory antibody. The recent outbreak of COVID-19 infected and killed thousands of people in the world. Rapid methods in finding peptides or antibody sequences that can inhibit the viral epitopes of SARS-CoV-2 will save the life of thousands. To predict neutralizing antibodies for SARS-CoV-2 in a high-throughput manner, in this paper, we use different machine learning (ML) model to predict the possible inhibitory synthetic antibodies for SARS-CoV-2. We collected 1933 virus-antibody sequences and their clinical patient neutralization response and trained an ML model to predict the antibody response. Using graph featurization with variety of ML methods, like XGBoost, Random Forest, Multilayered Perceptron, Support Vector Machine and Logistic Regression, we screened thousands of hypothetical antibody sequences and found nine stable antibodies that potentially inhibit SARS-CoV-2. We combined bioinformatics, structural biology, and Molecular Dynamics (MD) simulations to verify the stability of the candidate antibodies that can inhibit SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Large-scale serological testing in the population is essential to determine the true extent of the current SARS-CoV-2 pandemic. Serological tests measure antibody responses against pathogens and use predefined cutoff levels that dichotomize the quantitative test measures into sero-positives and negatives and use this as a proxy for past infection. With the imperfect assays that are currently available to test for past SARS-CoV-2 infection, the fraction of seropositive individuals in serosurveys is a biased estimator of the cumulative incidence and is usually corrected to account for the sensitivity and specificity. Here we use an inference method—referred to as mixture-model approach—for the estimation of the cumulative incidence that does not require to define cutoffs by integrating the quantitative test measures directly into the statistical inference procedure. We confirm that the mixture model outperforms the methods based on cutoffs, leading to less bias and error in estimates of the cumulative incidence. We illustrate how the mixture model can be used to optimize the design of serosurveys with imperfect serological tests. We also provide guidance on the number of control and case sera that are required to quantify the test's ambiguity sufficiently to enable the reliable estimation of the cumulative incidence. Lastly, we show how this approach can be used to estimate the cumulative incidence of classes of infections with an unknown distribution of quantitative test measures. This is a very promising application of the mixture-model approach that could identify the elusive fraction of asymptomatic SARS-CoV-2 infections. An R-package implementing the inference methods used in this paper is provided. Our study advocates using serological tests without cutoffs, especially if they are used to determine parameters characterizing populations rather than individuals. This approach circumvents some of the shortcomings of cutoff-based methods at exactly the low cumulative incidence levels and test accuracies that we are currently facing in SARS-CoV-2 serosurveys. Author summary: As other pathogens, SARS-CoV-2 elicits antibody responses in infected people that can be detected in their blood serum as early as a week after the infection until long after recovery. The presence of SARS-CoV-2 specific antibodies can therefore be used as a marker of past infection, and the prevalence of seropositive people, i.e. people with specific antibodies, is a key measure to determine the extent of the SARS-CoV-2 pandemic. The serological tests, however, are usually not perfect, yielding false positive and false negative results. Here we exploit an approach that refrains from classifying people as seropositive or negative, but rather compares the antibody level of an individual to that of confirmed cases and controls. This approach leads to more reliable estimates of cumulative incidence, especially for the low prevalence and low test accuracies that we face during the current SARS-CoV-2 pandemic. We also show how this approach can be extended to infer the presence of specific types of cases that have not been used for validating the test, such as people that underwent a mild or asymptomatic infection. [ABSTRACT FROM AUTHOR]

• The 0.5 ml vaccine was well tolerated in cats. • The 0.5 ml vaccine tended to result in less adverse local events. • The immunogenicity of the 0.5 ml vaccine is the same as the 1 ml vaccine. A non adjuvanted vaccine against feline herpesvirus, feline calicivirus, feline panleucopenia and feline leukemia has been formulated in reduced volume (0.5 ml) with the same antigen content as the conventional 1 ml presentation. This paper reports studies evaluating the safety and the immunogenicity of this reduced volume vaccine in comparison with the conventional volume vaccine. The safety of both vaccines was evaluated in a small sized laboratory trial. It was further tested in a randomized controlled field trial on a total of 398 cats. Immediate and delayed local and systemic adverse events were monitored after vaccination. The immunogenicity of each vaccine was also checked by serological antibody responses against the vaccines antigens during the laboratory trial. These studies showed that the 0.5 ml vaccine was well tolerated in cats, inducing less local events, while keeping the same immunogenicity as the corresponding 1 ml vaccine. Reducing the volume of the vaccine is a way to improve the convenience of administration and to help following vaccination guidelines with the aim of reducing the incidence of adverse events following vaccination. [ABSTRACT FROM AUTHOR]

Background: Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. Methods: For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results: 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. Conclusion: A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised. [ABSTRACT FROM AUTHOR]

Background: In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger. Methods: This research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes. Results: The analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p < 0.0001). Conclusion: The research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity. [ABSTRACT FROM AUTHOR]

Background: Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods: Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results: 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions: Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised. [ABSTRACT FROM AUTHOR]

This paper studies the global stability of a discrete-time pathogen dynamic model with both cell-mediated and antibody immune responses. Both latently and actively infected cells are incorporated into the model. We discretize the continuous-time model by using the nonstandard finite difference (NSFD) method. We establish that NSFD preserves the nonnegativity and boundedness of the solutions of the model. We derive four threshold parameters which govern the existence and stability of the steady states. We establish by using the Lyapunov method, the global stability of the five steady states of the model. We illustrate our theoretical results by using numerical simulations. [ABSTRACT FROM AUTHOR]

At present, secondary immune deficiencies have become a clinical problem, recognized in different specialties. The aim of this paper was to increase awareness and support the need for screening at-risk populations. Secondary immune deficiencies result in variety of conditions, but not all of them require immunoglobulin replacement therapy, as specific antibody response might be preserved. Moreover, the management of secondary immune deficiencies vary between countries and different medical disciplines. This literature review presents the most common causes and clinical presentation of secondary immunodeficiencies with predominant impaired antibody production. We present diagnostic guidelines for patients at-risk, with an emphasis on the role of prophylactic vaccination as a treatment and diagnostic tool. This review considers the specificity and disparities of the Polish healthcare system and ultimately, suggests that management teams should include a clinical immunologist experienced in the treatment of humoral immunodeficiencies. [ABSTRACT FROM AUTHOR]

A longstanding philosophical premise perceives simplicity as a desirable attribute of scientific theories. One of several raised justifications for this notion is that simple theories are more likely to indicate the true makeup of natural systems. Qualitatively parsimonious hypotheses and theories keep to a minimum the number of different postulated entities within a system. Formulation of such ontologically simple working hypotheses proved to be useful in the experimental probing of narrowly defined bio systems. It is less certain, however, whether qualitatively parsimonious theories are effective indicators of the true nature of complex biological systems. This paper assesses the success of ontologically simple theories in envisaging the makeup of three complex systems in bacteriology, immunology, and molecular biology. Evidence shows that parsimonious theories completely misconstrued the actual ontologically complex constitutions of the three examined systems. Since evolution and selective pressures typically produce ontologically intricate rather than simple bio systems, qualitatively parsimonious theories are mostly inapt indicators of the true nature of complex biological systems. [ABSTRACT FROM AUTHOR]

We present a flexible, open source R package designed to obtain biological and epidemiological insights from serological datasets. Characterising past exposures for multi-strain pathogens poses a specific statistical challenge: observed antibody responses measured in serological assays depend on multiple unobserved prior infections that produce cross-reactive antibody responses. We provide a general modelling framework to jointly infer infection histories and describe immune responses generated by these infections using antibody titres against current and historical strains. We do this by linking latent infection dynamics with a mechanistic model of antibody kinetics that generates expected antibody titres over time. Our aim is to provide a flexible package to identify infection histories that can be applied to a range of pathogens. We present two case studies to illustrate how our model can infer key immunological parameters, such as antibody titre boosting, waning and cross-reaction, as well as latent epidemiological processes such as attack rates and age-stratified infection risk. Author summary: Antibody levels can determine previous exposure to a pathogen and how likely individuals are to be infected in the future. However, antibody concentrations change over time, and some pathogens are continually evolving. In such cases, individuals may be infected and vaccinated multiple times when their pre-existing immunity fails, leading to a wide range of antibody profiles. Traditional approaches to analyse such data do not typically account for this. In addition, studies collecting antibody data may be designed differently, but are often underpinned by similar biological processes. We developed a statistical method and accompanying software package to better understand the immunology and epidemiology of these complex systems using serological data. We present two case studies to demonstrate how our software package, serosolver, can be applied to different settings: i) the epidemiology of the 2009 pandemic A/H1N1 influenza virus in Hong Kong and ii) historical patterns of A/H3N2 influenza infection in Guangzhou, China. These results demonstrate how modern analytical methods can reveal additional information from serological data that is otherwise missed using traditional approaches. [ABSTRACT FROM AUTHOR]

Malaria is one of the most dangerous diseases that threatens people's lives around the world. In this paper, we study a reaction-diffusion model for the within-host dynamics of malaria infection with an antibody immune response. The model is given by a system of partial differential equations (PDEs) to describe the blood-stage of malaria life cycle. It addresses the interactions between uninfected red blood cells, antibodies, and three types of infected red blood cells, namely ring-infected red blood cells, trophozoite-infected red blood cells and schizont-infected red blood cells. Moreover, the model contains a parameter to measure the efficacy of isoleucine starvation and its effect on the growth of malaria parasites. We show the basic properties of the model. We compute all equilibria and derive the thresholds from the conditions of existence of malaria equilibrium points. We prove the global stability of all equilibrium points based on choosing suitable Lyapunov functionals. We use the characteristic equations to verify the local instability of equilibrium points. We finally execute numerical simulations to validate the theoretical results and highlight some important observations. The results indicate that isoleucine starvation can have a critical impact on the stability of equilibrium points. When the efficacy of isoleucine starvation is high, it switches the system from the infection state to the malaria-free state. The presence of an antibody immune response does not lead to the elimination of malaria infection, but it suppresses the growth of malaria parasites and increases the amount of healthy red blood cells. [ABSTRACT FROM AUTHOR]

This paper investigates the global dynamics of Chikungunya virus (CHIKV) infection model with antibody immune response. We incorporate two ways of transmissions CHIKV-to-cell and cell-to-cell. We incorporate three types of discrete time delays into the model. The first time delay is the time between CHIKV entry an uninfected monocyte to become latent infected. The second time delay is the time between CHIKV entry on uninfected monocyte and the production of immature CHIKV. The third time delay represents the CHIKV's maturation time. Nonnegativity and boundedness properties of the solutions are proven. Further, global stability of the equilibria is established by constructing Lyapunov functions and by applying applying LaSalle's invariance principle. [ABSTRACT FROM AUTHOR]

Anti-GAD antibody syndrome is a result of the production of antibodies against glutamic acid decarboxylase (GAD), the main enzyme responsible for the production of gamma-aminobutyric acid (GABA). Several neurological manifestations including cerebellar ataxia and stiff person syndrome have been reported in association with anti-GAD antibodies. In this paper, we present a case of a young woman with anti-GAD antibodies who initially presented with cerebellar ataxia followed by stiff person syndrome three and a half years later. Having both cerebellar ataxia and stiff person syndrome is a rare occurrence in anti-GAD antibody syndrome. We emphasise the importance of long-term follow-up of patients with anti-GAD antibody syndrome, as delayed neurological manifestations can occur. [ABSTRACT FROM AUTHOR]

Pre- as well as post-exposure prophylaxis plays an important role in controlling the number of deaths associated with human rabies. Rabies vaccines, classically injected intramuscularly, are now also administered by intradermal (ID) route. Vaccines to be administered by the ID route should meet the same quality, safety and efficacy specifications as vaccines for intramuscular (IM) use. The aim of this paper is to provide information based on publicly available data regarding the ID use of rabies vaccines and to identify potential needs for further analysis of the potency, immunogenicity and effectiveness of rabies vaccines administered by this route. A first literature search, focused on the immunogenicity of rabies vaccines given by ID route, identified 338 publications in the period 1997–2018, 40 of which were included in our analyses. A second search investigating the effectiveness of ID vaccination resulted in 371 hits for the period 2007–2018, of which 13 suitable publications were retained. The immunogenicity of current rabies vaccines was analyzed in 3 ways: proportion of subjects reaching the antibody threshold of 0.5 IU/ml after ID vaccination, relationship between potency and immunogenicity of the vaccine given intradermally, and comparison of antibody responses after IM or ID vaccination. Overall, vaccines administered intradermally were found immunogenic. Post-exposure prophylaxis by ID route appeared at least as immunogenic as by IM regimens. By contrast, ID pre-exposure prophylaxis trended towards lower antibody titers than IM vaccination, but the observation was not associated with any clinical relevance. Vaccine effectiveness was assessed by investigating survival after exposure. Data from more than 30,000 patients who sought rabies post-exposure prophylaxis did not indicate that current vaccines administered by ID route lack efficacy. These results support current recommendations for ID vaccination against rabies. However, published data on ID performance were associated with significant weaknesses that future research should better address. [ABSTRACT FROM AUTHOR]

A growing number of tick species have now been demonstrated to induce red meat allergies through biting humans. During the course of the bite, Galactose alpha-1,3-Galactose, commonly abbreviated as alpha-Gal, a carbohydrate not found in humans, but common in four-legged mammals, makes its way through to the bloodstream, triggering antibody production. Subsequent consumption of red meat by bite victims sets off a peculiarly delayed immunological reaction that may range from hives through to anaphylaxis. This paper documents the discovery of its linkage with tick bites. The spread of this syndrome worldwide warrants the attention of scientific and clinical librarians serving allergists, immunologists, dieticians, and entomologists. [ABSTRACT FROM AUTHOR]

The fully synthetic humanized phage antibody library has the advantages including the minimized immunogenicity, which frequently happened in hybridoma cell-based antibody production. In this paper, using the constructed diverse complementarity determining region gene library and the germline gene as the backbone, we constructed eight single-chain antibody libraries and a combinatorial antibody library with a big capacity of 1.41 × 1010. M13EEA helper phage that was engineered from M13KO7 was applied to prepare phage antibody library. The eukaryotic expression of T-cell immune receptor with Ig and ITIM domain (TIGIT) antigen was used as a target antigen for screening. The screening of antigen-specific single-chain Fc-fused protein was performed through evaluation of binding affinity based on ELISA analysis. The IgG antibody was prepared with the screened single-chain protein. Finally, the CB3 antibody was screened out which exhibits the highest binding affinity with TIGIT with the Kd value of 8.155 × 10−10 M. The schematic illustrates the procedure of selection of TIGIT-specific human monoclone antibody with high specificity and binding activity. [ABSTRACT FROM AUTHOR]

In this paper, we propose and investigate a reaction–diffusion virus infection model with humoral immunity and nonlinear incidence. In spatially heterogeneous case, the basic reproduction number of virus infection R 0 is calculated, when R 0 ≤ 1 the global asymptotical stability of the infection-free steady state is established, and when R 0 > 1 the uniform persistence of infected cells and viruses, as well as the existence of antibody-free infection steady state are also obtained. In spatially homogeneous case, the antibody response basic reproduction number R 1 is calculated, by using the Lyapunov functions method and the persistence theory of dynamical systems we obtain that when R 0 > 1 and R 1 ≤ 1 the antibody-free infection equilibrium is globally asymptotically stable, and when R 0 > 1 and R 1 > 1 the model is uniformly persistent and the infection equilibrium exists and is also globally asymptotically stable. Finally, the numerical examples are presented in order to verify the validity of our theoretical results. [ABSTRACT FROM AUTHOR]

This paper studies the global dynamics of a general pathogenic infection model with two ways of infections. The effect of antibody immune response is analyzed. We incorporate three discrete time delays and both latently infected cells and actively infected cells. The infection rate and production and clearance/death rates of the cells and pathogens are given by general functions. We determine two threshold parameters to investigate the global stability of three equilibria. We use Lyapunov method to establish the global stability. We support our theoretical results by numerical simulations. [ABSTRACT FROM AUTHOR]

• Natural antibodies (NAb) binding not-self antigens in kid serum are shown. • The synthetic hapten 2,4,6-trinitrophenyl (TNP) presents the higher immunoreactivity to Nab. • IgM-NAb and total IgM levels are highly correlated within each sampling time. • IgG- and IgM-NAb levels are correlated only on the 1st and the second sampling time. • Specific antibody response (SpAb) is not related to NAb and Ig levels. Natural antibodies (NAb) are antibodies that can bind to a particular antigen without any apparent antigenic stimulation. In this paper, a careful analysis has been carried out on NAb levels in goat kid serum; possible correlations with the total immunoglobulin (tot-Ig) levels and specific antibody (SpAb) response were considered. Twenty randomly chosen kids were submitted to a first blood sampling (day 0). After 60 and 100 days, new blood samplings were carried out in the same animals. On day 0, after blood collection, all animals were immunized with a commercial vaccine; the immunization was repeated 30 days apart. Some exogenous antigens were tested to verify their immunoreactivity to NAb. Among them, the synthetic hapten 2,4,6-trinitrophenyl (TNP) conjugated with bovine serum albumin, resulted as the antigen with the higher immunoreactivity to NAb. Tot-Ig levels increased over time (p < 0.001). On the contrary, NAb levels, both IgG- and IgM-isotypes, significantly decreased during the experimental period (p < 0.001 and <0.05, respectively). Linear regression analyses showed a high correlation between IgM-NAb and tot-IgM levels (p < 0.001) at all the evaluated sampling times. However, a significant correlation between IgG-NAb and IgM-NAb was found only at the 1st (p < 0.01) and at the 2nd sampling (p < 0.05). No significant correlations were found between SpAb response and the other assessed humoral immune parameters. The obtained results are discussed in the light of the possible use of NAb assessment for the evaluation of the immune system activity in goat. [ABSTRACT FROM AUTHOR]

In this paper, the dynamical behaviours for a five-dimensional virus infection model with three delays which describes the interactions of antibody, cytotoxic T-lymphocyte (CTL) immune responses and Beddington-DeAngelis incidence are investigated. The reproduction numbers for virus infection, antibody immune response, CTL immune response, CTL immune competition and antibody immune competition, respectively, are calculated. By using the Lyapunov functionals and linearization method, the threshold conditions on the local and global stability of the equilibria for infection-free, immune-free, antibody response, CTL response and interior, respectively, are established. The existence of Hopf bifurcation with immune delay as a bifurcation parameter is investigated by using the bifurcation theory. Numerical simulations are presented to justify the analytical results. [ABSTRACT FROM AUTHOR]

• Model-assisted approaches for continuous chromatograph were reviewed. • Model-assisted methods for process development were focused and discussed. • Strategies for model-assisted process characterization was proposed. • Current model-assisted process design approaches were reviewed. • Perspectives of model-assisted tools for the future digitalized manufacturing were discussed. Continuous manufacturing in monoclonal antibody production has generated increased interest due to its consistent quality, high productivity, high equipment utilization, and low cost. One of the major challenges in realizing continuous biological manufacturing lies in implementing continuous chromatography. Given the complex operation mode and various operation parameters, it is challenging to develop a continuous process. Due to the process parameters being mainly determined by the breakthrough curves and elution behaviors, chromatographic modeling has gradually been used to assist in process development and characterization. Model-assisted approaches could realize multi-parameter interaction investigation and multi-objective optimization by integrating continuous process models. These approaches could reduce time and resource consumption while achieving a comprehensive and systematic understanding of the process. This paper reviews the application of modeling tools in continuous chromatography process development, characterization and design. Model-assisted process development approaches for continuous capture and polishing steps are introduced and summarized. The challenges and potential of model-assisted process characterization are discussed, emphasizing the need for further research on the design space determination strategy and parameter robustness analysis method. Additionally, some model applications for process design were highlighted to promote the establishment of the process optimization and process simulation platform. [ABSTRACT FROM AUTHOR]

The importance of B cells and their critical role in the maintenance of health through generation of antibody-mediated immune protection is undoubted. However, the differences between the responses of B cells with different surface phenotypes in different microanatomical sites as well as diversity in B-cell function outside antibody production are just starting to be acknowledged and resolved. This series of reviews and papers that focus on human B cells will be divided across two issues. The first part of the review series in this issue captures practical information on identifying B-cell subtypes in blood in health and inflammatory diseases as well as describing aspects of B-cell diversity depending on immunoglobulin isotype and microanatomical context. It also explores our current understanding of cytokine production by human B cells and the effect of obesity on the B-cell response. The last review in this issue will reflect on the important lessons learned from the SARS-CoV-2 pandemic; in particular the role of antigen availability and its effect on B-cell memory and antibody production. [ABSTRACT FROM AUTHOR]