scholarly journals Emergence of SARS-CoV-2 resistance mutations in a patient who received anti-SARS-COV2 spike protein monoclonal antibodies: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Honorine Fenaux ◽  
Romain Gueneau ◽  
Amal Chaghouri ◽  
Benoît Henry ◽  
Lina Mouna ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Case Report ◽  
Spike Protein ◽  
Immunosuppressed Patient ◽  
Optimal Management ◽  
Prevention Measures ◽  
Resistance Mutations ◽  
Case Presentation ◽  
Therapeutic Monoclonal Antibodies

Abstract Background To manage severe or potentially severe cases of CoronaVirus Disease 2019 (COVID-19), therapeutic monoclonal antibodies targeting Spike protein of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been designed. It has been noted in vitro that upon exposure to these treatments, mutations could be selected. Case presentation We here report the case of an immunosuppressed patient infected with a B.1.1.7 variant, who received a combination of monoclonal antibodies, and subsequently selected mutations K417N, E484K and Q493R on Spike protein of SARS-CoV-2. Conclusions Our case raises the importance of monitoring SARS-CoV-2 mutations in patients receiving monoclonal antibodies and having persistent excretion of the virus, in order to offer optimal management of their infection, and strengthen prevention measures to avoid subsequent transmission of these selected variants.

scholarly journals Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Urai Chaisri ◽  
Wanpen Chaicumpa
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza A ◽  
Treatment Strategies ◽  
Passive Immunization ◽  
Single Chain ◽  
Effector Functions ◽  
Single Chain Antibodies ◽  
Therapeutic Monoclonal Antibodies

This narrative review article summarizes past and current technologies for generating antibodies for passive immunization/immunotherapy. Contemporary DNA and protein technologies have facilitated the development of engineered therapeutic monoclonal antibodies in a variety of formats according to the required effector functions. Chimeric, humanized, and human monoclonal antibodies to antigenic/epitopic myriads with less immunogenicity than animal-derived antibodies in human recipients can be producedin vitro. Immunotherapy with ready-to-use antibodies has gained wide acceptance as a powerful treatment against both infectious and noninfectious diseases. Influenza, a highly contagious disease, precipitates annual epidemics and occasional pandemics, resulting in high health and economic burden worldwide. Currently available drugs are becoming less and less effective against this rapidly mutating virus. Alternative treatment strategies are needed, particularly for individuals at high risk for severe morbidity. In a setting where vaccines are not yet protective or available, human antibodies that are broadly effective against various influenza subtypes could be highly efficacious in lowering morbidity and mortality and controlling unprecedented epidemic/pandemic. Prototypes of human single-chain antibodies to several conserved proteins of influenza virus with no Fc portion (hence, no ADE effect in recipients) are available. These antibodies have high potential as a novel, safe, and effective anti-influenza agent.

scholarly journals Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies

2021 ◽  
Author(s):  
Alexander Wilhelm ◽  
Marek Widera ◽  
Katharina Grikscheit ◽  
Tuna Toptan ◽  
Barbara Schenk ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
Spike Protein ◽  
Cell Mediated Immunity ◽  
Treatment Variant

AbstractDue to numerous mutations in the spike protein, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) raises serious concerns since it may significantly limit the antibody-mediated neutralization and increase the risk of reinfections. While a rapid increase in the number of cases is being reported worldwide, until now there has been uncertainty about the efficacy of vaccinations and monoclonal antibodies. Our in vitro findings using authentic SARS-CoV-2 variants indicate that in contrast to the currently circulating Delta variant, the neutralization efficacy of vaccine-elicited sera against Omicron was severely reduced highlighting T-cell mediated immunity as essential barrier to prevent severe COVID-19. Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab, genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat COVID-19 due to Omicron and other emerging variants of concern.

scholarly journals B.1.526 SARS-CoV-2 Variants Identified in New York City are Neutralized by Vaccine-Elicited and Therapeutic Monoclonal Antibodies

mBio ◽  
2021 ◽  
Author(s):  
Hao Zhou ◽  
Belinda M. Dcosta ◽  
Marie I. Samanovic ◽  
Mark J. Mulligan ◽  
Nathaniel R. Landau ◽  
...  
Keyword(s):  
New York ◽  
Monoclonal Antibody ◽  
New York City ◽  
Monoclonal Antibodies ◽  
York City ◽  
Antibody Therapy ◽  
Spike Protein ◽  
Monoclonal Antibody Therapy ◽  
Therapeutic Monoclonal Antibodies

A novel SARS-CoV-2 variant termed B.1.526 was recently identified in New York City and has been found to be spreading at an alarming rate. The variant has mutations in its spike protein that might allow it to escape neutralization by vaccine-elicited antibodies and might cause monoclonal antibody therapy for COVID-19 to be less successful.

scholarly journals Neutralizing Monoclonal Anti-SARS-CoV-2 Antibodies Isolated from Immunized Rabbits Define Novel Vulnerable Spike-Protein Epitope

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 566
Author(s):  
Efi Makdasi ◽  
Yinon Levy ◽  
Ron Alcalay ◽  
Tal Noy-Porat ◽  
Eran Zahavy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Single Cells ◽  
High Specificity ◽  
Spike Protein ◽  
Course Of Disease ◽  
Recent Emergence ◽  
Escape Mutants ◽  
Immune Diagnostics

Monoclonal antibodies represent an important avenue for COVID-19 therapy and are routinely used for rapid and accessible diagnosis of SARS-CoV-2 infection. The recent emergence of SARS-CoV-2 genetic variants emphasized the need to enlarge the repertoire of antibodies that target diverse epitopes, the combination of which may improve immune-diagnostics, augment the efficiency of the immunotherapy and prevent selection of escape-mutants. Antigen-specific controlled immunization of experimental animals may elicit antibody repertoires that significantly differ from those generated in the context of the immune response mounted in the course of disease. Accordingly, rabbits were immunized by several recombinant antigens representing distinct domains of the viral spike protein and monoclonal antibodies were isolated from single cells obtained by cell sorting. Characterization of a panel of successfully isolated anti-receptor binding domain (RBD) and anti-N-terminal domain (NTD) antibodies demonstrated that they exhibit high specificity and affinity profiles. Anti-RBD antibodies revealing significant neutralizing potency against SARS-CoV-2 in vitro were found to target at least three distinct epitopes. Epitope mapping established that two of these antibodies recognized a novel epitope located on the surface of the RBD. We suggest that the antibodies isolated in this study are useful for designing SARS-CoV-2 diagnosis and therapy approaches.

scholarly journals The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2

2021 ◽  
Author(s):  
Andrea L. Cathcart ◽  
Colin Havenar-Daughton ◽  
Florian A. Lempp ◽  
Daphne Ma ◽  
Michael Schmid ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Host Cells ◽  
Infection Model ◽  
Dual Function ◽  
Resistance Mutations ◽  
Viral Respiratory Infection ◽  
Dual Action

ABSTRACTVIR-7831 and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VIR-7831 and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in the Fc region to prolong serum half-life and potentially enhance distribution to the respiratory mucosa. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. VIR-7831 and VIR-7832 potently neutralize live wild-type SARS-CoV-2 in vitro as well as pseudotyped viruses encoding spike protein from the B.1.1.7, B.1.351 and P.1 variants. In addition, they retain activity against monoclonal antibody resistance mutations that confer reduced susceptibility to currently authorized mAbs. The VIR-7831/VIR-7832 epitope does not overlap with mutational sites in the current variants of concern and continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with VIR-7831 had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that VIR-7831 and VIR-7832 are promising new agents in the fight against COVID-19.

scholarly journals Case Report: Mediastinal Mass in SARS-COV-2 Pandemic: A Word of Caution

2021 ◽  
Vol 8 ◽  
Author(s):  
Alessandro Baisi ◽  
Alessandra Mazzucco ◽  
Giovanni Caffarena ◽  
Gerardo Cioffi ◽  
Angelo Guttadauro ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Case Report ◽  
Mediastinal Mass ◽  
Lymphoproliferative Disease ◽  
Optimal Management ◽  
New Disease ◽  
Surgical Biopsy ◽  
Case Presentation ◽  
Vein Thrombosis ◽  
Deep Vein

Background: SARS-CoV-2 is a new disease with some manifestations not yet well-known. Sharing experiences in this topic is crucial for the optimal management of the patients.Case Presentation: Left upper extremity deep vein thrombosis (UEDVT) due to a mediastinal mass strongly suspected of lymphoproliferative disease in a patient affected by SARS-CoV-2, disappearing at the resolution of the viral infection.Conclusion: Before proceeding to surgical biopsy, mediastinal mass in SARS-CoV-2 patients must be revaluated after the resolution of the infection.

scholarly journals An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies

2021 ◽  
Author(s):  
Laura A VanBlargan ◽  
John M Errico ◽  
Peter Halfmann ◽  
Seth J Zost ◽  
James E. Crowe ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Development ◽  
Spike Protein ◽  
Clinical Use ◽  
Receptor Binding Domain ◽  
Antigenic Sites ◽  
Recent Emergence ◽  
Therapeutic Monoclonal Antibodies ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic resulting in millions of deaths worldwide. Despite the development and deployment of highly effective antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. Indeed, the recent emergence of the highly-transmissible B.1.1.529 Omicron variant is especially concerning because of the number of mutations, deletions, and insertions in the spike protein. Here, using a panel of anti-receptor binding domain (RBD) monoclonal antibodies (mAbs) corresponding to those with emergency use authorization (EUA) or in advanced clinical development by Vir Biotechnology (S309, the parent mAbs of VIR-7381), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Lilly (LY-CoV555 and LY-CoV016), and Celltrion (CT-P59), we report the impact on neutralization of a prevailing, infectious B.1.1.529 Omicron isolate compared to a historical WA1/2020 D614G strain. Several highly neutralizing mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost inhibitory activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (~12-fold decrease, COV2-2196 and COV2-2130 combination) or minimally affected (S309). Our results suggest that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.1.529 Omicron variant and related strains.

scholarly journals In vitro and in vivo preclinical studies predict REGEN-COV protection against emergence of viral escape in humans

2021 ◽  
Author(s):  
Richard Copin ◽  
Alina Baum ◽  
Elzbieta Wloga ◽  
Kristen E. Pascal ◽  
Stephanie Giordano ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Option ◽  
Viral Escape ◽  
Spike Protein ◽  
In Vivo Studies ◽  
Preclinical Studies ◽  
Global Pandemic ◽  
Emerging Virus

SummaryMonoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. As rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of minor virus variants in SARS-COV-2 isolates found in nature or identified from preclinical in vitro and in vivo studies and in the clinic. This study demonstrates that a combination of noncompeting antibodies not only provides full coverage against currently circulating variants but also protects against emergence of new such variants and their potential seeding into the population in a clinical setting.

scholarly journals Convalescent-Phase Sera and Vaccine-Elicited Antibodies Largely Maintain Neutralizing Titer against Global SARS-CoV-2 Variant Spikes

mBio ◽  
2021 ◽  
Author(s):  
Takuya Tada ◽  
Belinda M. Dcosta ◽  
Marie I. Samanovic ◽  
Ramin S. Herati ◽  
Amber Cornelius ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Rapid Evolution ◽  
Spike Protein ◽  
Convalescent Phase ◽  
Therapeutic Monoclonal Antibodies

The rapid evolution of SARS-CoV-2 variants has raised concerns with regard to their potential to escape from vaccine-elicited antibodies and anti-spike protein monoclonal antibodies. We report here on an analysis of sera from recovered patients and vaccinated individuals and on neutralization by Regeneron therapeutic monoclonal antibodies.

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