Neutralizing Monoclonal Antibody: New Member of Therapeutic Armamentarium Against COVID-19

2021 ◽  
Vol 11 (Number 2) ◽  
pp. 78-87
Author(s):  
Z H M Nazmul Alam ◽  
Ishrat Tahsin
Keyword(s):  
Monoclonal Antibody ◽  
Recombinant Proteins ◽  
Risk Groups ◽  
Target Population ◽  
Spike Protein ◽  
Passive Immunotherapy ◽  
Neutralizing Monoclonal Antibody ◽  
Optimal Deployment ◽  
Clinical Questions ◽  
New Treatments

Many targeted treatment methods have focused on SARS-CoV-2's spike protein, along with neutralizing monoclonal antibodies (mAbs), which are recombinant proteins, may be employed as a kind of passive immunotherapy to reduce pathogenicity. While vaccines are still the best way to prevent COVID-19 infection, mAbs are an effective treatment for those who have already been infected, as well as having the potential to prevent infection in those who have already been exposed to SARS-CoV-2, which can be especially beneficial to certain high-risk groups. Due to the limited initial availability of these new treatments, it is essential to consider their larger potential and create methods for their optimal deployment in clinical practice. The objectives of this review is to answer the most commonly asked clinical questions from HCPs and patients about the target population, dose, interactions with other medicines and vaccines, duration of immunity, and variants.

scholarly journals Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

2020 ◽  
Author(s):  
Rebecca L. Brocato ◽  
Lucia M. Principe ◽  
Robert K. Kim ◽  
Xiankun Zeng ◽  
Janice A. Williams ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Animal Models ◽  
Adaptive Immunity ◽  
Protective Efficacy ◽  
Severe Disease ◽  
Clinical Signs ◽  
Spike Protein ◽  
Syrian Hamsters ◽  
Viral Loads ◽  
Neutralizing Monoclonal Antibody

AbstractAnimal models recapitulating human COVID-19 disease, especially with severe disease, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease.One Sentence SummaryAn antibody targeting the spike protein of SARS-CoV-2 limits infection in immunosuppressed Syrian hamster models.

scholarly journals A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein

2017 ◽  
Vol 6 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Yingzhu Chen ◽  
Shuai Lu ◽  
Hao Jia ◽  
Yao Deng ◽  
Jianfang Zhou ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Spike Protein ◽  
Terminal Domain ◽  
Neutralizing Monoclonal Antibody ◽  
Antibody Targeting

scholarly journals pH-Induced Conformational Change of the Rotavirus VP4 Spike: Implications for Cell Entry and Antibody Neutralization

2005 ◽  
Vol 79 (13) ◽  
pp. 8572-8580 ◽  
Author(s):  
Joseph B. Pesavento ◽  
Sue E. Crawford ◽  
Ed Roberts ◽  
Mary K. Estes ◽  
B. V. Venkataram Prasad
Keyword(s):  
Monoclonal Antibody ◽  
Sialic Acid ◽  
Conformational Change ◽  
Cell Entry ◽  
Spike Protein ◽  
Cell Binding ◽  
Ph Changes ◽  
Multiple Receptors ◽  
Neutralizing Monoclonal Antibody ◽  
Dependent Cell

ABSTRACT The rotavirus spike protein, VP4, is a major determinant of infectivity and neutralization. Previously, we have shown that trypsin-enhanced infectivity of rotavirus involves a transformation of the VP4 spike from a flexible to a rigid bilobed structure. Here we show that at elevated pH the spike undergoes a drastic, irreversible conformational change and becomes stunted, with a pronounced trilobed appearance. These particles with altered spikes, at a normal pH of 7.5, despite the loss of infectivity and the ability to hemagglutinate, surprisingly exhibit sialic acid (SA)-independent cell binding in contrast to the SA-dependent cell binding exhibited by native virions. Remarkably, a neutralizing monoclonal antibody that remains bound to spikes throughout the pH changes (pH 7 to 11 and back to pH 7) completely prevents this conformational change, preserving the SA-dependent cell binding and hemagglutinating functions of the virion. A hypothesis that emerges from the present study is that high-pH treatment triggers a conformational change that mimics a post-SA-attachment step to expose an epitope recognized by a downstream receptor in the rotavirus cell entry process. This process involves sequential interactions with multiple receptors, and the mechanism by which the antibody neutralizes is by preventing this conformational change.

scholarly journals A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein

2017 ◽  
Vol 6 (1) ◽  
pp. 1-1 ◽  
Author(s):  
Yingzhu Chen ◽  
Shuai Lu ◽  
Hao Jia ◽  
Yao Deng ◽  
Jianfang Zhou ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Spike Protein ◽  
Terminal Domain ◽  
Neutralizing Monoclonal Antibody ◽  
Antibody Targeting

A Factor VIII Neutralizing Monoclonal Antibody and a Human Inhibitor Alloantibody Recognizing Epitopes in the C2 Domain Inhibit Factor VIII Binding to von Willebrand Factor and to Phosphatidylserine

1993 ◽  
Vol 69 (03) ◽  
pp. 240-246 ◽  
Author(s):  
Midori Shima ◽  
Dorothea Scandella ◽  
Akira Yoshioka ◽  
Hiroaki Nakai ◽  
Ichiro Tanaka ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Amino Acid ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Light Chain ◽  
Amino Acid Residues ◽  
Amino Terminal ◽  
Neutralizing Monoclonal Antibody ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryA neutralizing monoclonal antibody, NMC-VIII/5, recognizing the 72 kDa thrombin-proteolytic fragment of factor VIII light chain was obtained. Binding of the antibody to immobilized factor VIII (FVIII) was completely blocked by a light chain-specific human alloantibody, TK, which inhibits FVIII activity. Immunoblotting analysis with a panel of recombinant protein fragments of the C2 domain deleted from the amino-terminal or the carboxy-terminal ends demonstrated binding of NMC-VIII/5 to an epitope located between amino acid residues 2170 and 2327. On the other hand, the epitope of the inhibitor alloantibody, TK, was localized to 64 amino acid residues from 2248 to 2312 using the same recombinant fragments. NMC-VIII/5 and TK inhibited FVIII binding to immobilized von Willebrand factor (vWF). The IC50 of NMC-VIII/5 for the inhibition of binding to vWF was 0.23 μg/ml for IgG and 0.2 μg/ml for F(ab)'2. This concentration was 100-fold lower than that of a monoclonal antibody NMC-VIII/10 which recognizes the amino acid residues 1675 to 1684 within the amino-terminal portion of the light chain. The IC50 of TK was 11 μg/ml by IgG and 6.3 μg/ml by F(ab)'2. Furthermore, NMC-VIII/5 and TK also inhibited FVIII binding to immobilized phosphatidylserine. The IC50 for inhibition of phospholipid binding of NMC-VIII/5 and TK (anti-FVIII inhibitor titer of 300 Bethesda units/mg of IgG) was 10 μg/ml.

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