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

@article{Cathcart2021TheDF,
  title={The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2},
  author={Andrea L. Cathcart and Colin Havenar-Daughton and Florian A. Lempp and Da Ma and Michael Alexander Schmid and Maria L. Agostini and Barbara Guarino and Julia di Iulio and Laura E. Rosen and Heather Tucker and Josh R Dillen and Sambhavi Subramanian and Barbara Sloan and Siro Bianchi and Dora Pinto and Christian Saliba and Katja Culap and Jason A Wojcechowskyj and Julia Noack and Jiayi Zhou and Hannah Kaiser and Arthur Chase and Martin Montiel-Ruiz and Exequiel Dellota and Arnold Park and Roberto Spreafico and Anna Sahakyan and Elvin J Lauron and Nadine Czudnochowski and Elisabetta Cameroni and Sarah Ledoux and Adam D. Werts and Christophe Colas and Leah Soriaga and Amalio Telenti and Lisa A. Purcell and Seungmin Hwang and Gyorgy Snell and Herbert W. Virgin and Davide Corti and Christy M. Hebner},
  journal={bioRxiv},
  year={2021}
}
VIR-7831 (sotrovimab) 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. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been… 
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies
TLDR
It is suggested that several, but not all, of the antibodies in clinical use may lose efficacy against the B.1.1 .1.529 Omicron variant.
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies
TLDR
It is suggested that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.
In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate
TLDR
The results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.
Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape
TLDR
This work comprehensively characterize escape, breadth, and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD), including S3094, the parental antibody of the late-stage clinical antibody VIR-7831.
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
TLDR
It is shown that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2, marking a major SARS-CoV-2 mutational shift.
Antibodies to the SARS-CoV-2 receptor-binding domain that maximize breadth and resistance to viral escape
TLDR
This work comprehensively characterize escape, breadth, and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD) and identifies epitopes and features to prioritize for antibody and vaccine development against the current and potential future pandemics.
Antibody cocktail effective against variants of SARS-CoV-2
TLDR
These antibody cocktails are highly promising candidate tools for controlling new SARS-CoV-2 variants, including Delta, and exhibited potent prophylactic and therapeutic effects in Delta Sars-Cov-2 variant-infected hamsters.
Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants
TLDR
Some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus are reviewed.
Anti-SARS-CoV-2 human antibodies retaining neutralizing activity against SARS-CoV-2 B.1.1.529 (omicron)
TLDR
Data indicate that mAb 3B8 may have the potential to become a game-changer in the fight against the continuously evolving SARS-CoV-2, and three mAbs from this panel retain neutralizing activity against both delta and omicron.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 145 REFERENCES
Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies.
TLDR
As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.
SARS-CoV-2 variants show resistance to neutralization by many monoclonal and serum-derived polyclonal antibodies
TLDR
As several antibodies binding specific regions of the RBD and NTD show loss-of-neutralization potency in vitro against emerging variants, updated mAb cocktails, targeting of highly conserved regions, enhancement of mAb potency, or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.
Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody
TLDR
A directed evolution approach was employed to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency, and one of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarBecoviruses with high potency.
Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016
TLDR
It is suggested that future efforts should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.
Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions and monocytes for optimal therapeutic protection
SARS-CoV-2 has caused the global COVID-19 pandemic. Although passively delivered neutralizing antibodies against SARS-CoV-2 show promise in clinical trials, their mechanism of action in vivo is
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
TLDR
Several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which was identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS- coV) in 2003, and one antibody (named S309) potently neutralization, which may limit the emergence of neutralization-escape mutants.
Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
TLDR
These complete escape maps enable immediate interpretation of the consequences of mutations observed during viral surveillance and reveal that mutations escaping each individual antibody are already present in circulating SARS-CoV-2 strains.
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
TLDR
This work investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails.
...
1
2
3
4
5
...