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.

scholarly journals Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters

mBio ◽  
2021 ◽  
Author(s):  
Wen Su ◽  
Sin Fun Sia ◽  
Aaron J. Schmitz ◽  
Traci L. Bricker ◽  
Tyler N. Starr ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Fc Receptor ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Syrian Hamsters ◽  
Convalescent Phase ◽  
Main Target

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs).

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 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 SARS-CoV-2 Variants and Their Relevant Mutational Profiles: Update Summer 2021

2021 ◽  
Author(s):  
Mohammad Alkhatib ◽  
Valentina Svicher ◽  
Romina Salpini ◽  
Francesca Alessandra Ambrosio ◽  
Maria Concetta Bellocchi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Spike Protein ◽  
Convalescent Phase ◽  
Recurrent Mutations

Since the emergence of SARS-CoV-2, several recurrent mutations, particularly in the spike protein, arose during human-to-human transmission or spillover events between humans and animals, generating distinct worrisome variants of concern (VOCs) or of interest (VOIs), designated as such due to their clinical and diagnostic impacts. Characterizing these variants and their related mutations is important in tracking SAR-CoV-2 evolution and understanding the efficacy of vaccines and therapeutics based on monoclonal antibodies, convalescent-phase sera, and direct antivirals.

scholarly journals SARS-CoV-2 Omicron variant escapes neutralization by vaccinated and convalescent sera and therapeutic monoclonal antibodies

2021 ◽  
Author(s):  
Nariko Ikemura ◽  
Atsushi Hoshino ◽  
Yusuke Higuchi ◽  
Shunta Taminishi ◽  
Tohru Inaba ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Viral Escape ◽  
Spike Protein ◽  
The Novel ◽  
Neutralization Titer ◽  
Neutralization Activity ◽  
Therapeutic Drugs ◽  
Conserved Region ◽  
Therapeutic Monoclonal Antibodies

The novel SARS-CoV-2 variant, Omicron (B.1.1.529) contains about 30 mutations in the spike protein and the numerous mutations raise the concern of escape from vaccine, convalescent sera and therapeutic drugs. Here we analyze the alteration of their neutralizing titer with Omicron pseudovirus. Sera of 3 months after double BNT162b2 vaccination exhibite ~27-fold lower neutralization titers against Omicron than D614G mutation. Neutralization titer is also reduced in convalescent sera from Alpha and Delta patients. However, some Delta patients have relatively preserved neutralization activity up to the level of 3-month double BNT162b2 vaccination. Omicron escapes from the cocktail of imdevimab and casirivimab, whereas sotrovimab that targets the conserved region to prevent viral escape is effective to Omicron similarly to the original SARS-CoV-2. The ACE2 decoy is another modality that neutralize the virus independently of mutational escape and Omicron is also sensitive to the engineered ACE2.

scholarly journals The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies.

2021 ◽  
Author(s):  
Takuya Tada ◽  
Hao Zhou ◽  
Belinda M Dcosta ◽  
Marie I Samanovic ◽  
Mark J Mulligan ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Partial Resistance ◽  
Spike Protein ◽  
Therapeutic Monoclonal Antibodies ◽  
Antibody Cocktail ◽  
Spike Proteins

Highly transmissible SARS-CoV-2 variants recently identified in India designated B.1.617 and B.1.618 have mutations within the spike protein that may contribute to their increased transmissibility and that could potentially result in re-infection or resistance to vaccine-elicited antibody. B.1.617 encodes a spike protein with mutations L452R, E484Q, D614G and P681R while the B.1.618 spike has mutations Δ145-146, E484K and D614G. We generated lentiviruses pseudotyped by the variant proteins and determined their resistance to neutralization by convalescent sera, vaccine-elicited antibodies and therapeutic monoclonal antibodies. Viruses with B.1.617 and B.1.618 spike were neutralized with a 2-5-fold decrease in titer by convalescent sera and vaccine-elicited antibodies. The E484Q and E484K versions were neutralized with a 2-4-fold decrease in titer. Virus with the B.1.617 spike protein was neutralized with a 4.7-fold decrease in titer by the Regeneron monoclonal antibody cocktail as a result of the L452R mutation. The modest neutralization resistance of the variant spike proteins to vaccine elicited antibody suggests that current vaccines will remain protective against the B.1.617 and B.1.618 variants.

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

2021 ◽  
Author(s):  
Laura VanBlargan ◽  
John Errico ◽  
Peter Halfmann ◽  
Seth Zost ◽  
James Crowe ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Spike Protein ◽  
Clinical Use ◽  
Receptor Binding Domain ◽  
Neutralizing Activity ◽  
Therapeutic Monoclonal Antibodies

Abstract The emergence of the highly-transmissible B.1.1.529 Omicron variant of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is concerning for antibody countermeasure efficacy because of the number of mutations in the spike protein. Here, we tested a panel of anti-receptor binding domain monoclonal antibodies (mAbs) corresponding to those in clinical use by Vir Biotechnology (S309, the parent mAb of VIR-7831 [Sotrovimab]), 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) for their ability to neutralize an infectious B.1.1.529 Omicron isolate. Several mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost neutralizing activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (COV2-2196 and COV2-2130 combination, ~12-fold decrease) or minimally affected (S309). Our results suggest that several, but not all, of the antibodies in clinical use may lose efficacy against the B.1.1.529 Omicron variant.

scholarly journals B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

2021 ◽  
Author(s):  
Hao Zhou ◽  
Belinda M. Dcosta ◽  
Marie I. Samanovic ◽  
Mark J. Mulligan ◽  
Nathaniel R. Landau ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Monoclonal Antibodies ◽  
York City ◽  
Point Mutations ◽  
Spike Protein ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Wide Spread ◽  
Therapeutic Monoclonal Antibodies

DNA sequence analysis recently identified the novel SARS-CoV-2 variant B.1.526 that is spreading at an alarming rate in the New York City area. Two versions of the variant were identified, both with the prevalent D614G mutation in the spike protein together with four novel point mutations and with an E484K or S477N mutation in the receptor binding domain, raising concerns of possible resistance to vaccine-elicited and therapeutic antibodies. We report that convalescent sera and vaccine-elicited antibodies retain full neutralizing titer against the S477N B.1.526 variant and neutralize the E484K version with a modest 3.5-fold decrease in titer as compared to D614G. The E484K version was neutralized with a 12-fold decrease in titer by the REGN10933 monoclonal antibody but the combination cocktail with REGN10987 was fully active. The findings suggest that current vaccines and therapeutic monoclonal antibodies will remain protective against the B.1.526 variants. The findings further support the value of wide-spread vaccination.

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.

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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