scholarly journals Potent neutralization of SARS-CoV-2 variants of concern by an antibody with a unique genetic signature and structural mode of spike recognition

2021 ◽  
Author(s):  
Kevin J Kramer ◽  
Nicole V Johnson ◽  
Andrea R Shiakolas ◽  
Naveenchandra Suryadevara ◽  
Sivakumar Periasamy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Structural Characteristics ◽  
Clinical Development ◽  
Clinical Treatment ◽  
Genetic Signature ◽  
Lead Candidate ◽  
Structural Mode ◽  
Potent Neutralization

The emergence of novel SARS-CoV-2 lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of COVID-19. Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the LIBRA-seq technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 showed potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryo-EM structure of 54042-4 in complex with the SARS-CoV-2 spike revealed an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses unique genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings motivate 54042-4 as a lead candidate for clinical development to counteract current and future SARS-CoV-2 VOCs.

scholarly journals Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition

Cell Reports ◽  
2021 ◽  
pp. 109784
Author(s):  
Kevin J. Kramer ◽  
Nicole V. Johnson ◽  
Andrea R. Shiakolas ◽  
Naveenchandra Suryadevara ◽  
Sivakumar Periasamy ◽  
...  
Keyword(s):  
Genetic Signature ◽  
Structural Mode ◽  
Potent Neutralization

scholarly journals Strategies for clinical development of monoclonal antibodies beyond first-in-human trials: tested doses and rationale for dose selection

2018 ◽  
Vol 118 (5) ◽  
pp. 679-697 ◽  
Author(s):  
Marie Viala ◽  
Marie Vinches ◽  
Marie Alexandre ◽  
Caroline Mollevi ◽  
Anna Durigova ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Clinical Development ◽  
Dose Selection ◽  
Human Trials

scholarly journals Interleukin-17 cytokines: Effectors and targets in psoriasis—A breakthrough in understanding and treatment

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Immo Prinz ◽  
Inga Sandrock ◽  
Ulrich Mrowietz
Keyword(s):  
Monoclonal Antibodies ◽  
Inflammatory Diseases ◽  
Clinical Development ◽  
Tissue Homeostasis ◽  
Central Position ◽  
Interleukin 17 ◽  
Line Treatment ◽  
First Line ◽  
Intercellular Network ◽  
First Line Treatment

The IL-17 cytokine family comprising IL-17A to IL-17F and receptor subunits IL-17RA to IL-17RE represents a genetically ancient intercellular network regulating local tissue homeostasis. Its pivotal role in antifungal defense and its central position in the pathogenesis of inflammatory diseases including psoriasis were discovered only relatively late in the early 2000s. Since the connection of dysregulated IL-17 and psoriasis pathogenesis turned out to be particularly evident, a number of monoclonal antibodies targeting IL-17 pathways have been approved and are used as first line treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, and further agents are currently in clinical development.

Strategies for clinical development of monoclonal antibodies beyond first-in-man trials: Tested doses and rationale for dose selection.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3040-3040
Author(s):  
Marie Vinches ◽  
Alice Cuenant ◽  
Marie Alexandre ◽  
Anna Durigova ◽  
Nadia Hayaoui ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Clinical Development ◽  
Dose Selection

scholarly journals Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529

2021 ◽  
Author(s):  
Tongqing Zhou ◽  
Lingshu Wang ◽  
John Misasi ◽  
Amarendra Pegu ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Structural Basis ◽  
Resistance Mutations ◽  
Binding Surface ◽  
New Variant ◽  
Rapid Spread ◽  
Structural Mechanisms ◽  
The Impact ◽  
Insight Into ◽  
Potent Neutralization

With B.1.1.529 SARS-CoV-2 variant's rapid spread and substantially increased resistance to neutralization by vaccinee and convalescent sera, monoclonal antibodies with potent neutralization are eagerly sought. To provide insight into effective neutralization, we determined cryo-EM structures and evaluated potent receptor-binding domain (RBD) antibodies for their ability to bind and neutralize this new variant. B.1.1.529 RBD mutations altered 16% of the RBD surface, clustering on a ridge of this domain proximal to the ACE2-binding surface and reducing binding of most antibodies. Significant inhibitory activity was retained, however, by select monoclonal antibodies including A19-58.1, B1-182.1, COV2-2196, S2E12, A19-46.1, S309 and LY-CoV1404, which accommodated these changes and neutralized B.1.1.529 with IC50s between 5.1-281 ng/ml, and we identified combinations of antibodies with potent synergistic neutralization. Structure-function analyses delineated the impact of resistance mutations and revealed structural mechanisms for maintenance of potent neutralization against emerging variants.

scholarly journals Research of dynamics of immune response indicators in patients with infectious mononucleosis caused by Epstein-Barr virus

2019 ◽  
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Infectious Mononucleosis ◽  
Structural Characteristics ◽  
Peripheral Blood Lymphocytes ◽  
Th2 Cells ◽  
Simultaneous Increase ◽  
Control Group ◽  
Barr Virus ◽  
Immune Parameters

Objective. The article is devoted to the study of the content of the main immune parameters in patients with infectious mononucleosis (IM) in the dynamics of the disease. Materials and methods. A clinical examination of IM patients (n = 60) and patients of the control group (n = 20) included the study of complaints, epidemiological history, history of disease and life, objective examination, standard instrumental and laboratory studies in dynamics, detection of EBV DNA in saliva and blood serum, and a comprehensive analysis of immune parameters. The main subpopulations of peripheral blood lymphocytes (CD3 +; CD4 +; CD8 +; CD16 +; CD8 + CD28 +; CD8 + CD28-; CD20 +; CD25 +) were determined by flow laser cytometry on a FACS-Calibur apparatus (USA) using monoclonal antibodies. For identification of INF-γ (Th1-cells), IL-4 (Th2-cells) in the cytoplasm of T-lymphocytes, monoclonal antibodies INF-γ-PC-5, IL-4-PE (eBioscience, Beckman Caulter, R & D System) were used. Results. A comprehensive study of the state of the subpopulations of reacting immune cells revealed significant violations of cellular parts of the immune response compared to the control group. It was established that the immune response in patients with IM during the height of the disease is characterized by an imbalance in the cell link (as evidenced by an increase in the content of CD3+, CD4+, and a simultaneous increase in the content of CD16+, CD25+). In the period of convalescence, violations have been identified that will persist without reaching the levels of the control group in a larger number of IM patients. Conclusion. The results obtained indicate significant changes in the structural characteristics of the cellular immunity system and the multidirectional immune response in IM. The progressive character of changes in immune parameters in IM indicates the formation of a secondary cellular immune imbalance, a change in the balance of immunoregulatory mediators towards the Th2 link during the formation of protracted and chronic forms of EBV-infection.

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