Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Publication

Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth.

Zhiqiang Ku | Xuping Xie | Jianqing Lin | Peng Gao | Bin Wu | Abbas El Sahili | Hang Su | Yang Liu | Xiaohua Ye | Eddie Yongjun Tan | Xin Li | Xuejun Fan | Boon Chong Goh | Wei Xiong | Hannah Boyd | Antonio E Muruato | Hui Deng | Hongjie Xia | Jing Zou | Birte K Kalveram | Vineet D Menachery | Ningyan Zhang | Julien Lescar | Pei-Yong Shi | Zhiqiang An
Nature communications | 2022

One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce emergence of antibody resistance. Here we engineer two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv)2 design (14-H-06) but not the CrossMAb design (14-crs-06) shows increased antigen-binding and virus-neutralizing activities against multiple SARS-CoV-2 variants as well as increased breadth of neutralizing activity compared to the cocktail. X-ray crystallography and cryo-EM reveal distinct binding models for individual cocktail antibodies, and computational simulations suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and multiple variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.

Pubmed ID: 36138032

Research resources used in this publication

None found

Additional research tools detected in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: HHSN272201600013C
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI134907
  • Agency: NIAID NIH HHS, United States
    Id: R43 AI145617
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001439

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

Vero (tool)

RRID:CVCL_0059

Cell line Vero is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus

View all literature mentions

C57BL/6JGpt-H11em1Cin(K18-hACE2)/Gpt (tool)

RRID:IMSR_GPT:T037657

Mus musculus with name C57BL/6JGpt-H11em1Cin(K18-hACE2)/Gpt from IMSR.

View all literature mentions

BALB/cAnNCrl (tool)

RRID:MGI:2683685

laboratory mouse with name BALB/cAnNCrl from MGI.

View all literature mentions

Vero C1008 (tool)

RRID:CVCL_0574

Cell line Vero C1008 is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus

View all literature mentions

About

The Stimulating Peripheral Activity to Relieve Conditions (SPARC) effort is the result of National Institutes of Health’s (NIH) drive to map out the neural circuitry responsible for visceral control in higher vertebrates. The SPARC Anatomy Working Group (SAWG) is responsible for the integrity of anatomical knowledge in SPARC

Recent News Entries

Contact Us

Maryann Martone, Ph.D.

Department of Neurosciences, School of Medicine

University of California, San Diego

About SciCrunch | Privacy Policy | Terms of Service

SciCrunch