Evidence map›Paper›PMID 41188882›Full record

ArticleVirology journal2025

Development of broadly neutralizing antibodies against Omicron variants from existing neutralizing antibodies in clinical trials.

Yongbo Huang, Zhimin Lin, Xueyan Guo, Fangfang Zhang, Yanqun Wang, Zhaoyong Zhang, Jiantao Chen, Lu Liu, Mengzhu Zhu, Yiting Li and 12 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Virology journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05162365 (A Safety, Tolerability, and Efficacy Study of IBI314 in Ambulatory Patients With COVID-19), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05162365 phase1 / phase2terminatednot on this map

A Safety, Tolerability, and Efficacy Study of IBI314 in Ambulatory Patients With COVID-19

TypeinterventionalSponsorInnovent Biologics (Suzhou) Co. Ltd.Ran2022 to 2022Enrolled248ConditionsCOVID-19ArmsIBI314, Placebo
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Yongbo Huang *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Zhimin Lin *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Xueyan Guo *State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Fangfang Zhang *Innovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Yanqun WangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Zhaoyong ZhangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Jiantao ChenState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Lu LiuInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Mengzhu ZhuInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Yiting LiInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Meng NiInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Zixian ZhenInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Zhihai WuInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Xiaomin LingInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Shuaixiang ZhouInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China.
Yin XiState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Yuheng YuState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Wenhua LiangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Jincun ZhaoState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Li LiInnovent Biologics (Suzhou) Co., Ltd, Suzhou, Jiangsu, China. li.li@innoventbio.com.
Jianxing HeState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. hejx@vip.163.com.
Ling SangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. sonysang999@vip.163.com.

Funding

Emergency Key Program of Guangzhou Laboratory EKPG21-17National Key R&D Program of China 2022YFC2504402National Natural Science Foundation of China 82270081Natural Science Foundation of Guangdong Province 2020A1515011459
6 · The paper itself

Abstract

backgroundThe introduction of new SARS-CoV-2 Omicron strains has made it extremely difficult to create broadly neutralizing antibodies (nAbs) with assured therapeutic potential. Currently approved neutralizing antibodies have displayed substantially decreased or abolished efficacy against emerging Omicron variants including XBB and BQ.1 Due to the potential of reinfection from new emerging VOCs, this emphasizes the urgent need for developing widely active mAbs that offer preventive and therapeutic advantages to high-risk patients. Here, we aimed to investigate the feasibility of redirecting existing mAbs which are in late-stage development in clinical trials against new variants of SARS-CoV-2.

methodsIn vitro affinity maturation libraries against BA.2 RBD were constructed based on neutralizing antibodies P5-22 and P14-44 developed by Innovent Biologics as components of IBI314 (ClinicalTrials.gov Identifier: NCT05162365). Yeast surface display and flow cytometry sorting were utilized to screen antibodies with improved affinity. The selected antibodies were characterized by binding kinetics analysis. Their neutralization potency against SARS-CoV-2 variants was evaluated by pseudovirus neutralization assay and focus reduction neutralization test. Bispecific antibodies were designed in different formats using affinitymatured Fabs. The prophylactic and therapeutic efficacy of antibodies were examined in hACE2 transgenic mice infected with BA.2.3.

resultsBy in vitro affinity maturation of two nAb P5-22 and P14-44, we obtained antibodies broadly neutralizing pre-Omicron strains and BA.1/BA.2 variants. A bispecific 2 + 2 antibody showed further neutralization potency against BA.4/BA.5 even XBB and BQ1.1. These bispecific antibodies showed potent therapeutic and prophylactic potency in authentic Omicron virus challenge in mouse models in vivo.

conclusionsTogether, our approach revealed the possibility of engineering of existing antibodies to broad-spectrum mAbs as potential therapeutic or prophylactic agents for COVID-19.

Indexed as

Antibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesCOVID-19SARS-CoV-2AnimalsAntibodies, MonoclonalFemaleHumansMiceNeutralization TestsSpike Glycoprotein, CoronavirusAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Affinity maturationBispecific antibodyBroadly neutralizing antibodyIBI314OmicronSARS-CoV-2

Identifiers

PMID41188882
PMCPMC12584199

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Registered trials

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