首页|Nanobodies with cross-neutralizing activity provide prominent therapeutic efficacy in mild and severe COVID-19 rodent models

Nanobodies with cross-neutralizing activity provide prominent therapeutic efficacy in mild and severe COVID-19 rodent models

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The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention for clinical patients.Here,we screened three alpacas-derived nanobodies(Nbs)with neutralizing activity from twenty RBD-specific Nbs.The three Nbs were fused with the Fc domain of human IgG,namely aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc,which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to RBD.They effectively neutralized SARS-CoV-2 pseudoviruses D614G,Alpha,Beta,Gamma,Delta,and Omicron sub-lineages BA.1,BA.2,BA.4,and BA.5 and authentic SARS-CoV-2 prototype,Delta,and Omicron BA.1,BA.2 strains.In mice-adapted COVID-19 severe model,intranasal administration of aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory tracts.In the COVID-19 mild model,aVHH-13-Fc,which represents the optimal neutralizing activity among the above three Nbs,effectively protected hamsters from the challenge of SARS-CoV-2 prototype,Delta,Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the lungs.In structural modeling of aVHH-13 and RBD,aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved epitopes.Taken together,our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2,including those Delta and Omicron variants which have evolved into global pandemic strains.

COVID-19SARS-CoV-2NanobodyBroad-spectrumTherapeuticRodent models

Qiuxue Han、Shen Wang、Zhenshan Wang、Cheng Zhang、Xinyue Wang、Na Feng、Tiecheng Wang、Yongkun Zhao、Hang Chi、Feihu Yan、Xianzhu Xia

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Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing,100021,China

Changchun Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Changchun,132122,China

Jiangsu Co-innovation Centre for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Yangzhou,225009,China

Jilin Province Youth Talent Support Project

QT202115

2023

中国病毒学
中国科学院武汉病毒研究所,中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子:0.393
ISSN:1674-0769
年,卷(期):2023.38(5)
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