Epitope mapping and structural analysis of the anti-Der p 1 monoclonal antibody: insight into therapeutic potential

AbstractThe exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili.

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Neutralizing antibodies against SARS-CoV-2: current understanding, challenge and perspective

Antibody Therapeutics ◽

10.1093/abt/tbaa028 ◽

2020 ◽

Vol 3 (4) ◽

pp. 285-299

Author(s):

Yang Huang ◽

Hui Sun ◽

Hai Yu ◽

Shaowei Li ◽

Qingbing Zheng ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Therapeutic Potential ◽

Therapeutic Interventions ◽

Viral Escape ◽

Global Burden ◽

Health Crisis ◽

The Us ◽

Preclinical And Clinical Studies ◽

Insight Into ◽

Rapid Emergence

Abstract The rapid emergence of Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) as a pandemic that presents an urgent human health crisis. Many SARS-CoV-2 neutralizing antibodies (NAbs) were developed with efficient therapeutic potential. NAbs-based therapeutics against SARS-CoV-2 are being expedited to preclinical and clinical studies with two antibody drugs, LY3819253 (LY-CoV555) and REGN-COV2 (REGN10933 and REGN10987), approved by the US Food and Drug Administration for emergency use authorization for treating COVID-19. In this review, we provide a systemic overview of SARS-CoV-2 specific or cross-reactive NAbs and discuss their structures, functions and neutralization mechanisms. We provide insight into how these NAbs specific recognize the spike protein of SARS-CoV-2 or cross-react to other CoVs. We also summarize the challenges of NAbs therapeutics such as antibody-dependent enhancement and viral escape mutations. Such evidence is urgently needed to the development of antibody therapeutic interventions that are likely required to reduce the global burden of COVID-19.

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Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽

10.3390/cells10010042 ◽

2020 ◽

Vol 10 (1) ◽

pp. 42

Author(s):

Xiaoyu Pu ◽

Siyang Ma ◽

Yan Gao ◽

Tiankai Xu ◽

Pengyu Chang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Radiation Damage ◽

Therapeutic Potential ◽

Damage Model ◽

Bioactive Substances ◽

Radiation Induced ◽

Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

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A Cronobacter turicensis O1 Antigen-Specific Monoclonal Antibody Inhibits Bacterial Motility and Entry into Epithelial Cells

Infection and Immunity ◽

10.1128/iai.02211-14 ◽

2014 ◽

Vol 83 (3) ◽

pp. 876-887 ◽

Cited By ~ 6

Author(s):

Kristina Schauer ◽

Angelika Lehner ◽

Richard Dietrich ◽

Ina Kleinsteuber ◽

Rocío Canals ◽

...

Keyword(s):

Monoclonal Antibody ◽

Epithelial Cells ◽

Foodborne Pathogen ◽

Antimicrobial Effect ◽

Infection Model ◽

Cell Agglutination ◽

Content Type ◽

O Antigen ◽

Lethal Infection ◽

Insight Into

Cronobacter turicensisis an opportunistic foodborne pathogen that can cause a rare but sometimes lethal infection in neonates. Little is known about the virulence mechanisms and intracellular lifestyle of this pathogen. In this study, we developed an IgG monoclonal antibody (MAb; MAb 2G4) that specifically recognizes the O1 antigen ofC. turicensiscells. The antilipopolysaccharide antibody bound predominantly monovalently to the O antigen and reduced bacterial growth without causing cell agglutination. Furthermore, binding of the antibody to the O1 antigen ofC. turicensiscells caused a significant reduction of the membrane potential which is required to energize flagellar rotation, accompanied by a decreased flagellum-based motility. These results indicate that binding of IgG to the O antigen ofC. turicensiscauses a direct antimicrobial effect. In addition, this feature of the antibody enabled new insight into the pathogenicity ofC. turicensis. In a tissue culture infection model, pretreatment ofC. turicensiswith MAb 2G4 showed no difference in adhesion to human epithelial cells, whereas invasion of bacteria into Caco-2 cells was significantly inhibited.

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Development and characterization of a monoclonal antibody blocking human TRPM4 channel

Scientific Reports ◽

10.1038/s41598-021-89935-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

See Wee Low ◽

Yahui Gao ◽

Shunhui Wei ◽

Bo Chen ◽

Bernd Nilius ◽

...

Keyword(s):

Monoclonal Antibody ◽

Rat Model ◽

Therapeutic Potential ◽

Monovalent Cation ◽

Transgenic Animal ◽

Cell Swelling ◽

Live Cells ◽

Prolonged Incubation ◽

Trpm4 Channel

AbstractTRPM4 is a calcium-activated non-selective monovalent cation channel implicated in diseases such as stroke. Lack of potent and selective inhibitors remains a major challenge for studying TRPM4. Using a polypeptide from rat TRPM4, we have generated a polyclonal antibody M4P which could alleviate reperfusion injury in a rat model of stroke. Here, we aim to develop a monoclonal antibody that could block human TRPM4 channel. Two mouse monoclonal antibodies M4M and M4M1 were developed to target an extracellular epitope of human TRPM4. Immunohistochemistry and western blot were used to characterize the binding of these antibodies to human TRPM4. Potency of inhibition was compared using electrophysiological methods. We further evaluated the therapeutic potential on a rat model of middle cerebral artery occlusion. Both M4M and M4M1 could bind to human TRPM4 channel on the surface of live cells. Prolonged incubation with TRPM4 blocking antibody internalized surface TRPM4. Comparing to M4M1, M4M is more effective in blocking human TRPM4 channel. In human brain microvascular endothelial cells, M4M successfully inhibited TRPM4 current and ameliorated hypoxia-induced cell swelling. Using wild type rats, neither antibody demonstrated therapeutic potential on stroke. Human TRPM4 channel can be blocked by a monoclonal antibody M4M targeting a key antigenic sequence. For future clinical translation, the antibody needs to be humanized and a transgenic animal carrying human TRPM4 sequence is required for in vivo characterizing its therapeutic potential.

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