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Annals of Medicine Dec 2023Mosquito-borne infections are of global health concern because of their rapid spread and upsurge, which creates a risk for coinfections. DENV and ZIKV are transmitted by...
INTRODUCTION
Mosquito-borne infections are of global health concern because of their rapid spread and upsurge, which creates a risk for coinfections. DENV and ZIKV are transmitted by and and are prevalent in Nigeria and neighbouring countries. However, their seroprevalence, burden, hidden endemicity and possible cocirculation are poorly understood in Nigeria.
METHODS
We conducted a cross-sectional study of 871 participants from three regions of Nigeria. All serum samples were analysed using malaria RDT and the immunoblot molecular diagnostic assay recomLine Tropical Fever for the presence of arboviral antibody serological marker IgG (Mikrogen Diagnostik, Neuried, Germany) with DENV and ZIKV Nonstructural protein 1 (NS 1), DENV and ZIKV Equad (variant of the envelope protein with designated mutations to increase specificity), according to the manufacturer's instructions.
RESULTS
The overall IgG antibody seropositivity against DENV-flavivirus was 44.7% (389/871); 95% CI (41.41-47.99), while ZIKV-flavivirus was 19.2% (167/871); 95% CI (0.16-0.21), and DENV-ZIKV-flavivirus cocirculation antibody seropositivity was 6.2%5 (54/871); 95% CI (0.6-0.7) in the three study regions of Nigeria. The study cohort presented similar clinical signs and symptoms of flaviviruses (DENV and ZIKV) in all three study regions.
CONCLUSION
This study highlighted an unexpectedly high antibody seropositivity, burden, hidden endemicity, and regional spread of mono- and co-circulating flaviviruses (DENV and ZIKV) in Nigeria.Key messagesDengue flavivirus sero-cross-reactivity drives antibody-dependent enhancement of ZIKV infection.Both viruses share common hosts (humans) and vectors (primarily Aedes aegypti), and are thus influenced by similar biological, ecological, and economic factors, resulting in epidemiological synergy.Additionally, the actual burden in epidemic and interepidemic periods is grossly or chronically unknown and underreported. Despite this trend and the potential public health threat, there are no reliable data, and little is known about these arboviral co-circulation infections.
Topics: Animals; Humans; Zika Virus Infection; Zika Virus; Cross-Sectional Studies; Nigeria; Seroepidemiologic Studies; Dengue; Dengue Virus; Antibodies, Viral; Immunoglobulin G
PubMed: 37074313
DOI: 10.1080/07853890.2023.2175903 -
Journal of Agricultural and Food... Feb 2024Flunixin (FLU) is a nonsteroidal drug that is widely used in animals, causing severe drug residues in animal-derived foods and environment. The development of...
Flunixin (FLU) is a nonsteroidal drug that is widely used in animals, causing severe drug residues in animal-derived foods and environment. The development of antibody-based rapid immunoassay methods is of great significance for the monitoring of FLU and its metabolite 5-hydroxyflunixin (5-FLU). We prepared monoclonal antibodies (mAbs) with different recognition spectra through FLU-keyhole limpet hemocyanin conjugates as immunogen coupled with antibody screening strategies. mAb5E6 and mAb6D7 recognized FLU with high affinity, and mAb2H5 and mAb4A4 recognized FLU and 5-FLU with broad specificity. Through evaluating the recognition of these mAbs against more than 11 structural analogues and employing computational chemistry, molecular docking, and molecular dynamics methodologies, we preliminarily determined the recognition epitope and recognition mechanism of these mAbs. Finally, an indirect competitive enzyme-linked immunosorbent assay for FLU based on mAb6D7 was developed, which exhibited limits of detection as low as 0.016-0.042 μg kg (L) in milk and muscle samples.
Topics: Animals; Antibody Formation; Molecular Docking Simulation; Immunoassay; Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Antibody Specificity; Clonixin
PubMed: 38197248
DOI: 10.1021/acs.jafc.3c07766 -
Journal of Chemical Information and... Nov 2023The electrostatic properties of proteins arise from the number and distribution of polar and charged residues. Electrostatic interactions in proteins play a critical...
The electrostatic properties of proteins arise from the number and distribution of polar and charged residues. Electrostatic interactions in proteins play a critical role in numerous processes such as molecular recognition, protein solubility, viscosity, and antibody developability. Thus, characterizing and quantifying electrostatic properties of a protein are prerequisites for understanding these processes. Here, we present PEP-Patch, a tool to visualize and quantify the electrostatic potential on the protein surface in terms of surface patches, denoting separated areas of the surface with a common physical property. We highlight its applicability to elucidate protease substrate specificity and antibody-antigen recognition and predict heparin column retention times of antibodies as an indicator of pharmacokinetics.
Topics: Static Electricity; Proteins; Antibodies; Solubility; Viscosity
PubMed: 37934909
DOI: 10.1021/acs.jcim.3c01490 -
Fish & Shellfish Immunology Sep 2023Antibody with high affinity and specificity to antigen has widely used as a tool to combat various diseases. The variable domain of immunoglobulin new antigen receptor... (Review)
Review
Antibody with high affinity and specificity to antigen has widely used as a tool to combat various diseases. The variable domain of immunoglobulin new antigen receptor (VNAR) naturally found in shark contains autonomous function as single-domain antibody. Due to its excellent characteristics, the small, non-complex, and highly stable have made shark VNAR can acquires the antigen-binding capability that might not be reached by conventional antibody. Phage display technology enables shark VNAR to be presented on the surface of phage, allowing the exploration of shark VNAR as an alternative antibody format to target antigens from various infectious diseases. The application of phage-displayed shark VNAR in antibody library and biopanning eventually leads to the discovery and isolation of antigen-specific VNARs with diagnostic and therapeutic potential towards infectious diseases. This review provides an overview of the shark VNAR antibody, the types of phage display technology with comparison to the other types of display system, as well as the application and case studies of phage-displayed shark VNAR antibodies against infectious diseases.
Topics: Animals; Sharks; Antibodies; Antigens; Communicable Diseases; Bacteriophages; Peptide Library
PubMed: 37541634
DOI: 10.1016/j.fsi.2023.108986 -
Archives of Pharmacal Research Jan 2024The emergence of antibody-drug conjugates (ADCs) as a potential therapeutic avenue in cancer treatment has garnered significant attention. By combining the selective... (Review)
Review
The emergence of antibody-drug conjugates (ADCs) as a potential therapeutic avenue in cancer treatment has garnered significant attention. By combining the selective specificity of monoclonal antibodies with the cytotoxicity of drug molecules, ADCs aim to increase the therapeutic index, selectively targeting cancer cells while minimizing systemic toxicity. Various ADCs have been licensed for clinical usage, with ongoing research paving the way for additional options. However, the manufacture of ADCs faces several challenges. These include identifying suitable target antigens, enhancing antibodies, linkers, and payloads, and managing resistance mechanisms and side effects. This review focuses on the strategies to overcome these hurdles, such as site-specific conjugation techniques, novel antibody formats, and combination therapy. Our focus lies on current advancements in antibody engineering, linker technology, and cytotoxic payloads while addressing the challenges associated with ADC development. Furthermore, we explore the future potential of personalized medicine, leveraging individual patients' molecular profiles, to propel ADC treatments forward. As our understanding of the molecular mechanisms driving cancer progression continues to expand, we anticipate the development of new ADCs that offer more effective and personalized therapeutic options for cancer patients.
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Neoplasms; Antibodies, Monoclonal; Antigens
PubMed: 38153656
DOI: 10.1007/s12272-023-01479-6 -
Analytica Chimica Acta Feb 2024Cancer is a leading cause of death worldwide, with metastasis playing a significant role. Circulating Tumour Cells (CTCs) can provide important real-time insights into...
BACKGROUND
Cancer is a leading cause of death worldwide, with metastasis playing a significant role. Circulating Tumour Cells (CTCs) can provide important real-time insights into tumour heterogeneity and clonal evolution, making them an important tool for early diagnosis and patient monitoring. Isolated CTCs are typically identified by immunocytochemistry using positive biomarkers (cytokeratin) and exclusion biomarkers (CD45). However, some white blood cell (WBC) populations can express low levels of CD45 and stain non-specifically for cytokeratin, increasing their risk of misclassification as CTCs. There is a clear need to improve CTC detection and enumeration criteria to unequivocally eliminate interfering WBC populations.
RESULTS
This study showed that, indeed, some granulocyte subpopulations expressed low levels of CD45 and stained non-specifically for cytokeratin, misidentifying them as CTCs. These same cells, however, strongly expressed CD15, allowing them to be identified as WBCs and excluded from CTC classification. Flow cytometry confirmed the specificity of the CD15 antibody for the granulocyte subpopulation. False positives were considerably reduced from 25 % to 0.2 % by double exclusion, combining a CD15 antibody with a highly specific CD45 antibody. Furthermore, complete elimination of potential false positives was achieved using double exclusion in combination with improved selection of cytokeratin antibody. The study emphasises the importance of a robust exclusion criteria and high antibody specificity in CTC immuno-assays for accurate identification of CTC candidates and thorough exclusion of interfering WBC subpopulations.
SIGNIFICANCE
This study demonstrated how misidentifying a granulocyte subpopulation can lead to inaccurate CTC evaluation. However, sensitivity and specificity of CTC identification may be improved by using high-performing antibodies and by including a second exclusion biomarker, in turn, allowing for a more comprehensive clinical application of CTCs.
Topics: Humans; Biomarkers, Tumor; Neoplastic Cells, Circulating; Flow Cytometry; Keratins
PubMed: 38220297
DOI: 10.1016/j.aca.2023.342165 -
Biochemistry. Biokhimiia Sep 2023Biotechnological and biomedical applications of antibodies have been on a steady rise since the 1980s. As unique and highly specific bioreagents, monoclonal antibodies... (Review)
Review
Biotechnological and biomedical applications of antibodies have been on a steady rise since the 1980s. As unique and highly specific bioreagents, monoclonal antibodies (mAbs) have been widely exploited and approved as therapeutic agents. However, the use of mAbs has limitations for therapeutic applications. Antibody fragments (AbFs) with preserved antigen-binding sites have a significant potential to overcome the disadvantages of conventional mAbs, such as heterogeneous tissue distribution after systemic administration, especially in solid tumors, and Fc-mediated bystander activation of the immune system. AbFs possess better biodistribution coefficient due to lower molecular weight. They preserve the functional features of mAbs, such as antigen specificity and binding, while at the same time, ensuring much better tissue penetration. An additional benefit of AbFs is the possibility of their production in bacterial and yeast cells due to the small size, more robust structure, and lack of posttranslational modifications. In this review, we described current approaches to the AbF production with recent examples of AbF synthesis in bacterial and yeast expression systems and methods for the production optimization.
PubMed: 37770388
DOI: 10.1134/S0006297923090018 -
Bioanalysis 2024To develop an assay format for detection of total anti-adeno-associated virus 2 (AAV2) antibodies with low capsid material consumption. An immune complex (IC) assay... (Review)
Review
To develop an assay format for detection of total anti-adeno-associated virus 2 (AAV2) antibodies with low capsid material consumption. An immune complex (IC) assay format was developed. The format is based on the formation of ICs in solution and their subsequent detection using an anti-AAV2 antibody for capture and an antibody against the study species IgG for detection. The feasibility of the IC assay for detection of preexisting and treatment-emergent anti-AAV2 antibodies was demonstrated in cynomolgus monkey and human serum samples, including samples from a preclinical study with AAV2-based therapies. The presented IC assay is an easy-to-perform total anti-AAV2 antibody assay that requires a small amount of unlabeled capsid material and provides an intrinsic specificity control.
Topics: Humans; Animals; Macaca fascicularis; Antibodies, Viral; Dependovirus; Capsid; Antigen-Antibody Complex
PubMed: 38497775
DOI: 10.4155/bio-2023-0254 -
Cancers Nov 2023Monoclonal antibodies (mAbs) have exhibited substantial potential as targeted therapeutics in cancer treatment due to their precise antigen-binding specificity. Despite... (Review)
Review
Monoclonal antibodies (mAbs) have exhibited substantial potential as targeted therapeutics in cancer treatment due to their precise antigen-binding specificity. Despite their success in tumor-targeted therapies, their effectiveness is hindered by their large size and limited tissue permeability. Camelid-derived single-domain antibodies, also known as nanobodies, represent the smallest naturally occurring antibody fragments. Nanobodies offer distinct advantages over traditional mAbs, including their smaller size, high stability, lower manufacturing costs, and deeper tissue penetration capabilities. They have demonstrated significant roles as both diagnostic and therapeutic tools in cancer research and are also considered as the next generation of antibody drugs. In this review, our objective is to provide readers with insights into the development and various applications of nanobodies in the field of cancer treatment, along with an exploration of the challenges and strategies for their prospective clinical trials.
PubMed: 38067344
DOI: 10.3390/cancers15235639 -
Nature Jun 2024Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on...
Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on untargeted chemotherapies and limited possibilities to treat malignant cells after HSCT without affecting the transplanted healthy cells. Antigen-specific cell-depleting therapies hold the promise of much more targeted elimination of diseased cells, as witnessed in the past decade by the revolution of clinical practice for B cell malignancies. However, target selection is complex and limited to antigens expressed on subsets of haematopoietic cells, resulting in a fragmented therapy landscape with high development costs. Here we demonstrate that an antibody-drug conjugate (ADC) targeting the pan-haematopoietic marker CD45 enables the antigen-specific depletion of the entire haematopoietic system, including HSCs. Pairing this ADC with the transplantation of human HSCs engineered to be shielded from the CD45-targeting ADC enables the selective eradication of leukaemic cells with preserved haematopoiesis. The combination of CD45-targeting ADCs and engineered HSCs creates an almost universal strategy to replace a diseased haematopoietic system, irrespective of disease aetiology or originating cell type. We propose that this approach could have broad implications beyond haematological malignancies.
Topics: Animals; Female; Humans; Male; Mice; Hematologic Neoplasms; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Immunoconjugates; Leukocyte Common Antigens; Cell Line, Tumor; Antibody Specificity
PubMed: 38778101
DOI: 10.1038/s41586-024-07456-3