Covalent dimerization of camelidae anti-human TNF-alpha single domain antibodies by the constant kappa light chain domain improves neutralizing activity

2010 ◽  
pp. n/a-n/a ◽  
Author(s):  
Martin Giersberg ◽  
Doreen M. Floss ◽  
Sergey Kipriyanov ◽  
Udo Conrad ◽  
Jürgen Scheller
Keyword(s):  
Light Chain ◽  
Single Domain ◽  
Tnf Alpha ◽  
Kappa Light Chain ◽  
Neutralizing Activity ◽  
Covalent Dimerization ◽  
Single Domain Antibodies

Transglutaminase-catalyzed covalent multimerization of camelidae anti-human TNF single domain antibodies improves neutralizing activity

2009 ◽  
Vol 142 (2) ◽  
pp. 170-178 ◽  
Author(s):  
Ingo Plagmann ◽  
Athena Chalaris ◽  
Andrei A. Kruglov ◽  
Sergei Nedospasov ◽  
Philip Rosenstiel ◽  
...  
Keyword(s):  
Single Domain ◽  
Neutralizing Activity ◽  
Single Domain Antibodies

scholarly journals Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Iebe Rossey ◽  
Morgan S. A. Gilman ◽  
Stephanie C. Kabeche ◽  
Koen Sedeyn ◽  
Daniel Wrapp ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Fusion Protein ◽  
Respiratory Tract Infections ◽  
Antiviral Agents ◽  
Single Domain ◽  
Neutralizing Activity ◽  
Inflammatory Monocytes ◽  
Single Domain Antibodies ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.

scholarly journals Single-domain antibodies efficiently neutralize SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Irina A Favorskaya ◽  
Dmitry V Shcheblyakov ◽  
Ilias B Esmagambetov ◽  
Inna V Dolzhikova ◽  
Irina A Alekseeva ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Neutralizing Antibodies ◽  
Treatment Options ◽  
Fold Increase ◽  
Single Domain ◽  
Drug Candidate ◽  
Receptor Binding Domain ◽  
Neutralizing Activity ◽  
Single Domain Antibodies ◽  
Alpha Beta

Virus-neutralizing antibodies are one of the few treatment options for COVID-19. The evolution of SARS-CoV-2 virus has led to the emergence of virus variants with reduced sensitivity to some antibody-based therapies. The development of potent antibodies with a broad spectrum of neutralizing activity is urgently needed. Here we isolated a panel of single-domain antibodies that specifically bind to the receptor-binding domain of SARS-CoV-2 S glycoprotein. Three of the selected antibodies exhibiting most robust neutralization potency were used to generate dimeric molecules. We observed that these modifications resulted in up to a 200-fold increase in neutralizing activity. The most potent heterodimeric molecule efficiently neutralized each of SARS-CoV-2 variant of concern, including Alpha, Beta, Gamma and Delta variants. This heterodimeric molecule could be a promising drug candidate for a treatment for COVID-19 caused by virus variants of concern.

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

2019 ◽  
Vol 18 (2) ◽  
pp. 176-182
Author(s):  
Chen Weiyan ◽  
Deng Wujian ◽  
Chen Songwei
Keyword(s):  
Acute Lung Injury ◽  
B Cells ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Light Chain ◽  
Cecal Ligation ◽  
Nuclear Factor ◽  
Kappa Light Chain ◽  
Cecal Ligation And Puncture ◽  
Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

scholarly journals Untranslated immunoglobulin kappa light chain mRNA in a lambda light chain-producing mouse myeloma, MOPC104E.

1980 ◽  
Vol 255 (11) ◽  
pp. 5291-5295
Author(s):  
T. Kataoka ◽  
M. Ono ◽  
M. Kawakami ◽  
Y. Ikawa ◽  
M. Aida ◽  
...  
Keyword(s):  
Light Chain ◽  
Kappa Light Chain ◽  
Lambda Light Chain ◽  
Immunoglobulin Kappa ◽  
Mouse Myeloma

Engineering of single-domain antibodies for next generation snakebite antivenoms

2021 ◽  
Author(s):  
Carla F.C. Fernandes ◽  
Soraya S. Pereira ◽  
Marcos B. Luiz ◽  
Nauanny K.R.L. Silva ◽  
Marcela Cristina da Silva ◽  
...  
Keyword(s):  
Single Domain ◽  
Next Generation ◽  
Single Domain Antibodies
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