scholarly journals Use of bacteriophage for discovery of therapeutically relevant antibodies against infectious diseases

2019 ◽  
Vol 40 (1) ◽  
pp. 33
Author(s):  
Martina L Jones
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Biology ◽  
Infectious Diseases ◽  
Phage Display ◽  
Clinical Use ◽  
Diagnostic Use ◽  
Inflammatory Conditions ◽  
Wide Range ◽  
Antibody Libraries ◽  
Bacteria Culture

Scientists George P Smith and Gregory Winter were recently awarded half of the 2018 Nobel Prize for Chemistry for developing a technology to display exogenous peptides and proteins on the surface of bacteriophage. ‘Phage display' has revolutionised the development of monoclonal antibodies, allowing fully human-derived antibodies to be isolated from large antibody libraries. It has been used for the discovery of many blockbuster drugs, including Humira (adalimumab), the highest selling drug yearly since 2012, with US$18.4b in sales globally in 20171. Phage display can be used to isolate antibodies to almost any antigen for a wide range of applications including clinical use (for cancer, inflammatory conditions and infectious diseases), diagnostic use or as research tools. The technology is accessible to any laboratory equipped for molecular biology and bacteria culture.

scholarly journals Characterization of Monoclonal Antibodies against Bovine herpesvirus type 1 selected by Phage Display Technology

2017 ◽  
Vol 38 (6) ◽  
pp. 3915
Author(s):  
Greice Japolla ◽  
Ana Flávia Batista Penido ◽  
Greyciele Rodrigues Almeida ◽  
Luiz Artur Mendes Bataus ◽  
Jair Pereira Cunha Junior ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Phage Display ◽  
Bovine Herpesvirus ◽  
Single Chain ◽  
Phage Display Technology ◽  
Herpesvirus Type ◽  
Wide Range ◽  
Display Technology ◽  
Bovine Herpesvirus Type 1

The specificity of monoclonal antibodies (mAbs) to desired targets makes these molecules suitable for therapeutic and diagnostic uses against a wide range of pathogens. Phage display antibody libraries offer one method by which mAbs can be selected for, without the use of conventional hybridoma technology. In this work, phage display technology was used to construct, select and characterize a combinatorial single chain fragment variable (scFv) antibody library against bovine herpesvirus type 1 (BoHV-1) from the immune repertoire of chickens immunized with the virus. In silico analysis of the hypervariable domains of the antibody heavy chains revealed a high frequency of scFv fragments with low variability, suggesting that selection had probably been carried out and favored by a few im-munogenic viral antigens. The reactivity of the scFv fragments selected against BoHV-1 was demon-strated by Phage-ELISA. A significant increase in antibody reactivity to the target was observed after six rounds of library selection, showing its potential use as a molecule for BoHV-1 diagnosis. The strategy described here opens up a field for the use of phage display as a tool for selection of mono-clonal antibodies that could be used for theranostic applications against infectious and parasitic dis-eases of veterinary interest.

The neutralization potency of anti-SARS-CoV-2 therapeutic human monoclonal antibodies is retained against novel viral variants

2021 ◽  
Author(s):  
Efi Makdasi ◽  
Anat Zvi ◽  
Ron Alcalay ◽  
Tal Noy-Porat ◽  
Eldar Peretz ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibodies ◽  
Receptor Binding ◽  
Clinical Use ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Human Monoclonal Antibodies ◽  
Wide Range ◽  
The Uk

SummaryA wide range of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) were reported to date, most of which target the spike glycoprotein and in particular its receptor binding domain (RBD) and N-terminal domain (NTD) of the S1 subunit. The therapeutic implementation of these antibodies has been recently challenged by the emerging SARS-CoV-2 variants, harboring an extensively-mutated spike versions. Consequently, the re-assessment of mAbs, previously reported to neutralize the original early-version of the virus, represents an assignment of high priority.With respect to the evolving mutations in the virus spike RBD, we evaluated the aptitude of four previously selected mAbs, targeting distinct epitopes, to bind RBD versions harboring individual mutations at positions 501, 477, 484, 439, 417 and 453. Mutations of these residues represent the prevailing worldwide distributed modifications of the RBD, previously reported to mediate escape from antibody neutralization. Additionally, the in vitro neutralization efficacies of the four RBD-specific mAbs, as well as two NTD-specific mAbs, were evaluated against two frequent SARS-CoV-2 variants of concern (VOCs): (i) the B.1.1.7 variant, emerged in the UK and (ii) the B.1.351 variant, emerged in South Africa. B.1.351, was previously suggested to escape many therapeutic mAbs, including those authorized for clinical use.The results of the present study, clearly indicate that in spite of mutation accumulation in the spike of the virus, some neutralizing mAbs preserve their potency to combat SARS-CoV-2 emerged variants. In particular, the previously reported highly potent MD65 mAb is shown to retain its ability to bind the prevalent novel viral mutations and to effectively neutralize the B.1.1.7 and B.1.351 variants of high clinical concern.

scholarly journals Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Kristian Daniel Ralph Roth ◽  
Esther Veronika Wenzel ◽  
Maximilian Ruschig ◽  
Stephan Steinke ◽  
Nora Langreder ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Infectious Diseases ◽  
Phage Display ◽  
Antibody Fragment ◽  
Recombinant Antibodies ◽  
Phage Display Libraries ◽  
Antibody Phage ◽  
Antibody Phage Display

Antibodies are essential molecules for diagnosis and treatment of diseases caused by pathogens and their toxins. Antibodies were integrated in our medical repertoire against infectious diseases more than hundred years ago by using animal sera to treat tetanus and diphtheria. In these days, most developed therapeutic antibodies target cancer or autoimmune diseases. The COVID-19 pandemic was a reminder about the importance of antibodies for therapy against infectious diseases. While monoclonal antibodies could be generated by hybridoma technology since the 70ies of the former century, nowadays antibody phage display, among other display technologies, is robustly established to discover new human monoclonal antibodies. Phage display is an in vitro technology which confers the potential for generating antibodies from universal libraries against any conceivable molecule of sufficient size and omits the limitations of the immune systems. If convalescent patients or immunized/infected animals are available, it is possible to construct immune phage display libraries to select in vivo affinity-matured antibodies. A further advantage is the availability of the DNA sequence encoding the phage displayed antibody fragment, which is packaged in the phage particles. Therefore, the selected antibody fragments can be rapidly further engineered in any needed antibody format according to the requirements of the final application. In this review, we present an overview of phage display derived recombinant antibodies against bacterial, viral and eukaryotic pathogens, as well as microbial toxins, intended for diagnostic and therapeutic applications.

scholarly journals Aptamers in the virologists' toolkit

2007 ◽  
Vol 88 (2) ◽  
pp. 351-364 ◽  
Author(s):  
William James
Keyword(s):  
Monoclonal Antibodies ◽  
Nucleic Acid ◽  
Molecular Biology ◽  
Virus Replication ◽  
Antiviral Agents ◽  
Gene Products ◽  
Free Process ◽  
Wide Range ◽  
Potential Applications

Aptamers are artificial nucleic acid ligands that can be generated in vitro against a wide range of molecules, including the gene products of viruses. Aptamers are isolated from complex libraries of synthetic nucleic acids by an iterative, cell-free process that involves repetitively reducing the complexity of the library by partitioning on the basis of selective binding to the target molecule, followed by reamplification. For virologists, aptamers have potential uses as tools to help to analyse the molecular biology of virus replication, as a complement to the more familiar monoclonal antibodies. They also have potential applications as diagnostic biosensors and in the development of antiviral agents. In recent years, these two promising avenues have been explored increasingly by virologists; here, the progress that has been made is reviewed.

scholarly journals Monoclonal Antibodies (mAbs) Approved for Cancer Treatment in the 2020s

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Pouya Safarzadeh Kozani ◽  
Abdolhossein Naseri ◽  
Pooria Safarzadeh Kozani ◽  
Sanaz Khatami ◽  
Abdolkarim Sheikhi
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Cancer Treatment ◽  
Solid Tumors ◽  
Viral Infections ◽  
Clinical Use ◽  
Wide Applicability ◽  
Wide Range

: Monoclonal antibodies are one of the most eminent types of immunotherapeutics that have taken over the biopharmaceutical market because they are approved for a wide range of cancers, either blood-based malignancies or solid tumors, and also non-cancer indications, from migraine to viral infections. Due to their wide applicability as immunotherapeutics, countless biopharmaceutical companies try to be in the competition by developing monoclonal antibodies and advancing into clinical trials with them. Since the approval of the first monoclonal antibodies, the speed of their discovery and approval for medical use have been rather incremental, so that the progress of this market has been anticipated to increase in the current decade. Herein, we take a look at some of the monoclonal antibodies, which have been approved for clinical use in the current decade, so far. Moreover, we underline the encouraging results from the clinical trials that led to the approval of these immunotherapeutics.

scholarly journals Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

2021 ◽  
pp. 074873042098732
Author(s):  
N. Kronfeld-Schor ◽  
T. J. Stevenson ◽  
S. Nickbakhsh ◽  
E. S. Schernhammer ◽  
X. C. Dopico ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Multidisciplinary Approach ◽  
Preliminary Assessment ◽  
Epidemiological Evidence ◽  
Wide Range ◽  
Human Coronaviruses ◽  
Induced Changes ◽  
And Behavior ◽  
Timing Phase

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

scholarly journals Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1781
Author(s):  
Gustavo A. Arias-Pinilla ◽  
Helmout Modjtahedi
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibodies ◽  
Antibody Therapy ◽  
Therapeutic Targets ◽  
Poor Response ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Western World ◽  
Wide Range ◽  
Novel Therapeutic

Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

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