scholarly journals High Efficacy of Therapeutic Equine Hyperimmune Antibodies Against SARS-CoV-2 Variants of Concern

2021 ◽  
Vol 8 ◽  
Author(s):  
Andres Moreira-Soto ◽  
Mauricio Arguedas ◽  
Hebleen Brenes ◽  
Willem Buján ◽  
Eugenia Corrales-Aguilar ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Costa Rica ◽  
Polyclonal Antibodies ◽  
Low Cost ◽  
High Efficacy ◽  
Low Concentrations ◽  
Alpha Beta ◽  
Therapeutic Monoclonal Antibodies ◽  
Treatment Alternatives

SARS-CoV-2 variants of concern show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies; therefore, treatment alternatives are needed. We tested therapeutic equine polyclonal antibodies (pAbs) that are being assessed in clinical trials in Costa Rica against five globally circulating variants of concern: alpha, beta, epsilon, gamma and delta, using plaque reduction neutralization assays. We show that equine pAbs efficiently neutralize the variants of concern, with inhibitory concentrations in the range of 0.146–1.078 μg/mL, which correspond to extremely low concentrations when compared to pAbs doses used in clinical trials. Equine pAbs are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

scholarly journals High efficacy of therapeutic equine hyperimmune antibodies against SARS CoV-2 variants of concern

2021 ◽  
Author(s):  
Andres Moreira-Soto ◽  
Mauricio Arguedas ◽  
Hebleen Brenes ◽  
Willem Buján ◽  
Eugenia Corrales-Aguilar ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Polyclonal Antibodies ◽  
Low Cost ◽  
High Efficacy ◽  
Alpha Beta ◽  
Therapeutic Monoclonal Antibodies

SARS-CoV-2 variants of concern (VoC) show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies. We tested therapeutic equine polyclonal antibodies (pAbs) against four VoC (alpha, beta, epsilon and gamma). We show that equine pAbs efficiently neutralize VoC, suggesting they are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

scholarly journals Prediction of Clearance of Monoclonal and Polyclonal Antibodies and Non-Antibody Proteins in Children: Application of Allometric Scaling

Antibodies ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 40
Author(s):  
Iftekhar Mahmood
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Prediction Error ◽  
Allometric Scaling ◽  
Polyclonal Antibodies ◽  
Therapeutic Proteins ◽  
Preterm Neonates ◽  
Pharmacokinetic Parameters ◽  
Pediatric Dose ◽  
Age Dependent

Allometric scaling can be used for the extrapolation of pharmacokinetic parameters from adults to children. The objective of this study was to predict clearance of therapeutic proteins (monoclonal and polyclonal antibodies and non-antibody proteins) allometrically in preterm neonates to adolescents. There were 13 monoclonal antibodies, seven polyclonal antibodies, and nine therapeutic proteins (non-antibodies) in the study. The clearance of therapeutic proteins was predicted using the age dependent exponents (ADE) model and then compared with the observed clearance values. There were in total 29 therapeutic proteins in this study with 75 observations. The number of observations with ≤30%, ≤50%, and >50% prediction error was 60 (80%), 72 (96%), and 3 (4%), respectively. Overall, the predicted clearance values of therapeutic proteins in children was good. The allometric method proposed in this manuscript can be used to select first-in-pediatric dose of therapeutic proteins in pediatric clinical trials.

scholarly journals Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 15 ◽  
Author(s):  
Francesca Bonello ◽  
Roberto Mina ◽  
Mario Boccadoro ◽  
Francesca Gay
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Plasma Cells ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Promising Target ◽  
Therapeutic Monoclonal Antibodies ◽  
Antibody Drug

Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs®), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.

scholarly journals Exploring antibody repurposing for COVID-19: beyond presumed roles of therapeutic antibodies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Puneet Rawat ◽  
Divya Sharma ◽  
Ambuj Srivastava ◽  
Vani Janakiraman ◽  
M. Michael Gromiha
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Effective Vaccine ◽  
Therapeutic Antibodies ◽  
Viral Neutralization ◽  
Investigational Drugs ◽  
Therapeutic Monoclonal Antibodies ◽  
Interaction Surface ◽  
Limited Choice

AbstractThe urgent need for a treatment of COVID-19 has left researchers with limited choice of either developing an effective vaccine or identifying approved/investigational drugs developed for other medical conditions for potential repurposing, thus bypassing long clinical trials. In this work, we compared the sequences of experimentally verified SARS-CoV-2 neutralizing antibodies and sequentially/structurally similar commercialized therapeutic monoclonal antibodies. We have identified three therapeutic antibodies, Tremelimumab, Ipilimumab and Afasevikumab. Interestingly, these antibodies target CTLA4 and IL17A, levels of which have been shown to be elevated during severe SARS-CoV-2 infection. The candidate antibodies were evaluated further for epitope restriction, interaction energy and interaction surface to gauge their repurposability to tackle SARS-CoV-2 infection. Our work provides candidate antibody scaffolds with dual activities of plausible viral neutralization and immunosuppression. Further, these candidate antibodies can also be explored in diagnostic test kits for SARS-CoV-2 infection. We opine that this in silico workflow to screen and analyze antibodies for repurposing would have widespread applications.

scholarly journals The Relevance of Monoclonal Antibodies in the Treatment of COVID-19

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 557
Author(s):  
Anabel Torrente-López ◽  
Jesús Hermosilla ◽  
Natalia Navas ◽  
Luis Cuadros-Rodríguez ◽  
José Cabeza ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
State Of The Art ◽  
Virus Protein ◽  
Immune Disorders ◽  
The Subject ◽  
New Treatments ◽  
Therapeutic Monoclonal Antibodies ◽  
Made In

Major efforts have been made in the search for effective treatments since the outbreak of the COVID-19 infection in December 2019. Extensive research has been conducted on drugs that are already available and new treatments are also under development. Within this context, therapeutic monoclonal antibodies (mAbs) have been the subject of widespread investigation focusing on two target-based groups, i.e., non-SARS-CoV-2 specific mAbs, that target immune system responses, and SARS-CoV-2 specific mAbs, designed to neutralize the virus protein structure. Here we review the latest literature about the use of mAbs in order to describe the state of the art of the clinical trials and the benefits of using these biotherapeutics in the treatment of COVID-19. The clinical trials considered in the present review include both observational and randomized studies. We begin by presenting the studies conducted using non-SARS-CoV-2 specific mAbs for treating different immune disorders that were already on the market. Within this group of mAbs, we focus particularly on anti-IL-6/IL-6R. This is followed by a discussion of the studies on SARS-CoV-2 specific mAbs. Our findings indicate that SARS-CoV-2 specific mAbs are significantly more effective than non-specific ones.

scholarly journals Platelet glycoprotein (Gp) IX associates with GpIb alpha in the platelet membrane GpIb complex

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2782-2787 ◽  
Author(s):  
G Wu ◽  
FJ Meloni ◽  
SS Shapiro
Keyword(s):  
Flow Cytometry ◽  
Monoclonal Antibodies ◽  
Synthetic Peptide ◽  
Polyclonal Antibodies ◽  
Platelet Membrane ◽  
Platelet Glycoprotein ◽  
Beta Subunits ◽  
Membrane Glycoprotein ◽  
Published Evidence ◽  
Alpha Beta

The platelet membrane glycoprotein (Gp) Ib complex consists of four polypeptides: the disulfide-linked GpIb alpha and GpIb beta subunits; GpIX, tightly, but noncovalently associated with GpIb alpha-beta; and the more weakly associated GpV. It is not certain whether the association of GpIX to Gplb alpha-beta is via GpIB alpha, GpIb beta, or both subunits, although recently published evidence implicates an interaction with GpIb beta. We have investigated the interaction of GpIX with GpIb alpha-beta using polyclonal rabbit antibodies to GpIb alpha and GpIb beta raised by immunization with purified glycocalicin and with synthetic peptide sequences from GpIb beta, respectively, as well as monoclonal antibodies directed against GpIX (FMC-25) and against GpIb alpha (AP-1). We performed two types of experiments, using either purified GpIb complex or platelets. (1) When wells were coated with nonreduced GpIb complex, the binding of FMC-25 was inhibited 73% by GpIb alpha antibody, but only 30% by the GpIb beta antibody; when wells were coated with reduced complex, FMC-25 binding was inhibited by the same two antibodies by 86% and 13%, respectively. When wells were coated with polyclonal GpIb alpha or GpIb beta antibodies and then incubated with reduced GpIb complex, only wells coated with GpIb alpha antibodies captured GpIX reactivity. When wells were coated with FMC-25 and then incubated with nonreduced GpIb complex, both the GpIb alpha and GpIb beta polyclonal antibodies reacted strongly; in contrast, only GpIb alpha reactivity was retained when wells coated with FMC-25 were incubated with reduced GpIb complex. In the reciprocal experiment, AP-1- coated wells incubated with either nonreduced or reduced GpIb complex bound radiolabeled FMC-25. (2) The ability of polyclonal GpIb alpha and GpIb beta antibodies to inhibit binding of FMC-25 to platelets was studied by ELISA and by flow cytometry. In both systems, FMC-25 binding was inhibited by the GpIb alpha antibody, but not significantly by the GpIb beta antibody. We conclude that GpIX is strongly associated with GpIb alpha in the purified platelet GpIb complex and in the platelet membrane.

scholarly journals Detection and Diagnosis of Xylella fastidiosa by Specific Monoclonal Antibodies

Agronomy ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
María Teresa Gorris ◽  
Antonio Sanz ◽  
Javier Peñalver ◽  
María M. López ◽  
Mario Colomer ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Real Time ◽  
Real Time Pcr ◽  
Polyclonal Antibodies ◽  
Xylella Fastidiosa ◽  
Low Cost ◽  
Kappa Index ◽  
Commercial Kits ◽  
O Antigens ◽  
Das Elisa

Monoclonal antibodies (MAb) specific to Xylella fastidiosa were obtained through hybridoma technology using heat-treated somatic O antigens from LMG 17159strain. Ten stable hybrydoma clones secreting MAb were selected and their isotype was determined. The MAbs 2G1/PPD, IgG1 showed specificity for X. fastidiosa, detecting all the analyzed strains representing different subspecies, STs and hosts. Polyclonal antibodies (PAb) against X. fastidiosa were also produced and antiserum 17159-O/IVIA was selected for the highest titre and its excellent detection capability. MAb 2G1/PPD was tested against strain IVIA 5235 in PBS and in spiked raw extract samples from almond, olive, citrus, and other hosts and its sensitivity by DAS-ELISA was 104 CFU mL−1. The MAb also reacted with high affinity and avidity against X. fastidiosa by DASI-ELISA and Tissue print-ELISA. The diagnostic parameters of DAS-ELISA based on MAb were calculated and compared with the gold standard real-time PCR. The diagnostic specificity of MAb2G1/PPD was 100%, the diagnostic sensitivity was 88.5% compared to Harper’s real-time PCR and 89.9% compared to Francis’ real-time PCR. The agreement between the techniques was almost perfect according to the estimated Cohen’s kappa-index, even in symptomless almond trees. The developed immunological techniques represent sustainable and low-cost analysis tools, based on specific, homogeneous, and well-characterized MAbs, which can be obtained in unlimited quantities in a reproducible way and constitute a guarantee for the standardization of commercial kits. They are a valuable option within a polyphasic strategy for the detection of X. fastidiosa.

An Immunoradiometric Assay for Factor VIII Related Antigen (VIIIRAg) Using Two Monoclonal Antibodies-Comparison with Polyclonal Rabbit Antibodies for Use in von Willebrand’s Disease Diagnosis

1984 ◽  
Vol 52 (03) ◽  
pp. 250-252 ◽  
Author(s):  
Y Sultan ◽  
Ph Avner ◽  
P Maisonneuve ◽  
D Arnaud ◽  
Ch Jeanneau
Keyword(s):  
Monoclonal Antibodies ◽  
Structural Changes ◽  
Polyclonal Antibodies ◽  
Disease Diagnosis ◽  
Immunoradiometric Assay ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Structural Abnormalities ◽  
Antigenic Material ◽  
Von Willebrand

SummaryTwo monoclonal antibodies raised against FVIII/von Willebrand protein were used in an immunoradiometric assay (IRMA) to measure this antigen in normal plasma and plasma of patients with different forms of von Willebrand’s disease. The first antibody, an IgG1 was used to coat polystyrene tubes, the second one, an IgG2a, iodinated and used in the second step. Both antibodies inhibit ristocetin induced platelet agglutination and react strongly with platelets, megacaryocytes and endothelial cells. The IRMA test using these antibodies showed greater sensitivity than that using rabbit polyclonal anti VIIIRAg antibodies. A good correlation between the two tests was nevertheless found when VIIIRAg was measured in the majority of patient’s plasma. However 5 patients from 3 different families showed more antigenic material in the rabbit antibody IRMA than in the monoclonal antibody IRMA. It is suggested therefore that the monoclonal antibodies identify part of the VIIIR:Ag molecule showing structural abnormalities in these vWd patients, these structural changes remaining undetected by the polyclonal antibodies.

Design of Innovative Therapeutic Monoclonal Antibodies

2017 ◽  
pp. 10-29
Author(s):  
A.V. Karabelskii ◽  
◽  
T.A. Nemankin ◽  
A.B. Ulitin ◽  
A.S. Vaganov ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Monoclonal Antibodies
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