Engineered bispecific antibodies with enhanced breadth and potency against SARS-CoV-2 variants and SARS-related coronaviruses

The concern of COVID-19 persists due to the continuous emergence of variants and the potential spillover of animal coronaviruses. The broad-spectrum neutralizing antibodies play a pivotal role in the prevention and treatment of coronavirus (CoV) infections. Here, we constructed 18 bi-specific antibo...

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Veröffentlicht in:Medical microbiology and immunology 2024-12, Vol.213 (1), p.24-24, Article 24
Hauptverfasser: Chang, Fangfang, Wu, Qian, Hu, Yabin, Pan, Zhendong, Liu, Yong-Chen, Li, Yue-Zhou, Bostina, Mihnea, Liu, Wenpei, Zhao, Ping, Qu, Xiaowang, Li, Yi-Ping
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container_issue 1
container_start_page 24
container_title Medical microbiology and immunology
container_volume 213
creator Chang, Fangfang
Wu, Qian
Hu, Yabin
Pan, Zhendong
Liu, Yong-Chen
Li, Yue-Zhou
Bostina, Mihnea
Liu, Wenpei
Zhao, Ping
Qu, Xiaowang
Li, Yi-Ping
description The concern of COVID-19 persists due to the continuous emergence of variants and the potential spillover of animal coronaviruses. The broad-spectrum neutralizing antibodies play a pivotal role in the prevention and treatment of coronavirus (CoV) infections. Here, we constructed 18 bi-specific antibodies (bsAbs) using 9 antibodies isolated from COVID-19 convalescents and vaccinated individuals, designed as dual variable domain immunoglobulin (DVD-Ig). A bsAb 5-HI showed a high binding capability to the S1 subunit of spike and exhibited breadth and potency against pseudotyped SARS-CoV-2 variants of concerns (VOCs) and SARS-related-CoVs (SARSr-CoVs), with half maximal effective concentration (EC 50 ) of 0.028–3.444 nM and 50% inhibitory concentration (IC 50 ) of 0.008-0.800 nM. In addition, it retained neutralization potency against the peudotyped virus of recently prevalent JN.1 strain (IC 50 , 12.74 nM). We found that the parental antibodies showed weak or no binding to the receptor binding domain (RBD) of the SARS-CoV, EG.5.1, and JN.1. However, the 5-HI maintained the binding with RBD and prevented the binding between hACE2 and RBD (IC 50 for the RBD of SARS-CoV, 1.067 nM; EG.5.1, 0.423 nM; JN.1, 0.223 nM). In neutralization assays with the authentic virus, we found that the 5-HI effectively neutralized Omicron variants XBB.1.5 (IC 50 , 0.308 nM), EG.5.1 (IC 50 , 0.129 nM), and JN.1 (IC 50 , 13.692 nM), while its parental antibodies showed weakened or no neutralization. Therefore, the 5-HI represents a promising candidate for further development in the treatment and prevention of ongoing evolved SARS-CoV-2 VOCs and other SARSr-CoVs that potentially emerge in the future.
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ispartof Medical microbiology and immunology, 2024-12, Vol.213 (1), p.24-24, Article 24
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subjects Animals
Antibodies
Antibodies, Bispecific - immunology
Antibodies, Bispecific - pharmacology
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Biomedical and Life Sciences
Biomedicine
Bispecific antibodies
Coronaviridae
Coronaviruses
COVID-19
COVID-19 - immunology
COVID-19 - virology
COVID-19 infection
domain
Humans
Immunoglobulins
Immunology
inhibitory concentration 50
median effective concentration
Medical Microbiology
neutralization
Neutralization Tests
Protein Engineering
SARS-CoV-2 - immunology
Severe acute respiratory syndrome coronavirus 2
Severe acute respiratory syndrome-related coronavirus
Severe acute respiratory syndrome-related coronavirus - immunology
Spike Glycoprotein, Coronavirus - immunology
Virology
viruses
title Engineered bispecific antibodies with enhanced breadth and potency against SARS-CoV-2 variants and SARS-related coronaviruses
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