Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2

@article{Zhang2021PotentAP,
  title={Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2},
  author={Qi Zhang and Bin Ju and Jiwan Ge and Jasper Fuk-Woo Chan and Lin Cheng and Ruoke Wang and Weijin Huang and Mengqi Fang and Peng Chen and Bingjie Zhou and Shuo Song and Sisi Shan and Baohua Yan and Senyan Zhang and Xiangyang Ge and Jiazhen Yu and Juanjuan Zhao and Haiyan Wang and Li Liu and Qining Lv and Lili Fu and Xuanling Shi and Kwok Yung Yuen and Lei Liu and Youchun Wang and Zhiwei Chen and Linqi Zhang and Xinquan Wang and Zheng Zhang},
  journal={Nature Communications},
  year={2021},
  volume={12}
}
Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share… 
Molecular analysis of a public cross-neutralizing antibody response to SARS-CoV-2
TLDR
It is reported here that the combination of germline genes IGHV2-5/IGLV2-14 represents a public antibody response to the receptor-binding domain (RBD) that potently cross-neutralizes all VOCs to date, including Omicron and its sub-lineages.
Structural basis of Omicron neutralization by affinity-matured public antibodies
TLDR
Public Sars-CoV-2 neutralizing antibodies can, without modified spike vaccines, mature to cross-neutralize exceptionally antigenically diverged SARS-Cov-2 variants, including Omicron.
A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
TLDR
P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants, withstanding the three key mutations found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA).
Molecular basis for antiviral activity of pediatric neutralizing antibodies targeting SARS-CoV-2 Spike receptor binding domain
TLDR
It is demonstrated that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients and the molecular determinants of the epitope-driven protection and VOC-evasion are revealed.
A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge
TLDR
ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants.
SARS-CoV-2 variants resist antibody neutralization and broaden host ACE2 usage
TLDR
A panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the Spike protein identified in the GISAID database are constructed.
Epistasis at the SARS-CoV-2 RBD Interface and the Propitiously Boring Implications for Vaccine Escape
TLDR
A computational approach is employed to assess the risk of antibody escape resulting from mutations in the receptor-binding domain of the spike protein of the wild type SARS-CoV-2 virus as well as the Gamma and Delta variants, indicating that emergence of escape mutants is somewhat less likely for the Delta variant than for the wildtype and moderately morelikely for the Gamma variant.
Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape
TLDR
The engineered antibodies showed increased in vitro functional activity in terms of neutralization potency and/or breadth ofneutralization against viral variants and suggest that monoclonal antibodies for anti-viral indications could benefit from in vitro affinity maturation to reduce viral escape pathways.
Delta variant (B.1.617.2) sublineages do not show increased neutralization resistance
TLDR
This study sought to determine whether Delta Plus and Delta-V differ from the Delta variant regarding cell entry and neutralization sensitivity by using rhabdoviral pseudotypes, which are adequate models for cell entry of SARS-CoV-2, and previously described monoclonal antibodies and sera/plasma from infected or BNT162b2/Comirnaty vaccinated individuals.
Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection
TLDR
Key points regarding mAb-based detection tests and treatments for the COVID-19 pandemic are highlighted.
...
...

References

SHOWING 1-10 OF 66 REFERENCES
Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
TLDR
This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.
Structural basis of a shared antibody response to SARS-CoV-2
TLDR
It is found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein, which is promising for vaccine design.
Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model
TLDR
A role for potent neutralizing antibodies (nAbs) in prophylaxis, and potentially therapy, of COVID-19 is suggested, as indicated by maintained weight and low lung viral titers in treated animals, and the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters.
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
TLDR
It is shown that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected.
Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike
TLDR
A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres, suggesting both of these regions at the top of the viral spike are immunogenic.
Potently neutralizing and protective human antibodies against SARS-CoV-2
TLDR
An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.
Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry
TLDR
One antibody, P2C-1F11, most closely mimics binding of receptor ACE2 and displays the most potent neutralizing activity in vitro, as well as conferring protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice.
mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.
TLDR
The results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.
SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
TLDR
Eight new structures of distinct COVID-19 human neutralizing antibodies 5 in complex with the SARS-CoV-2 spike trimer or RBD are solved and rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use are provided.
...
...