Potent monoclonal antibodies neutralize Omicron sublineages and other SARS-CoV-2 variants

被引：4

作者：

Chen, Zhaochun ^{[1
]}

Zhang, Peng ^{[2
]}

Matsuoka, Yumiko ^{[3
]}

Tsybovsky, Yaroslav ^{[4
]}

West, Kamille ^{[5
]}

Santos, Celia ^{[3
]}

Boyd, Lisa F. ^{[6
]}

Nguyen, Hanh ^{[1
]}

Pomerenke, Anna ^{[1
]}

Stephens, Tyler ^{[4
]}

Olia, Adam S. ^{[7
]}

Zhang, Baoshan ^{[7
]}

De Giorgi, Valeria ^{[5
]}

Holbrook, Michael R. ^{[8
]}

Gross, Robin ^{[8
]}

Postnikova, Elena ^{[8
]}

Garza, Nicole L. ^{[9
]}

Johnson, Reed F. ^{[9
]}

Margulies, David H. ^{[6
]}

Kwong, Peter D. ^{[7
]}

Alter, Harvey J. ^{[5
]}

Buchholz, Ursula J. ^{[3
]}

Lusso, Paolo ^{[2
]}

Farci, Patrizia ^{[1
]}

机构：

[1] NIAID, Hepat Pathogenesis Sect, Lab Infect Dis, NIH, Bethesda, MD 20892 USA

[2] NIAID, Lab Immunoregulat, NIH, Bethesda, MD USA

[3] NIAID, RNA Viruses Sect, Lab Infect Dis, NIH, Bethesda, MD USA

[4] Leidos Biomed Res Inc, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA

[5] NIH, Dept Transfus Med, Clin Ctr, Bethesda, MD USA

[6] NIAID, Mol Biol Sect, Lab Immune Syst Biol, NIH, Bethesda, MD USA

[7] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA

[8] NIAID, Integrated Res Facil, NIH, Frederick, MD USA

[9] NIAID, SARS CoV 2 Virol Core, Lab Viral Dis, NIH, Bethesda, MD USA

来源：

CELL REPORTS | 2022年 / 41卷 / 05期

基金：

美国国家卫生研究院;

关键词：

RECEPTOR-BINDING DOMAIN; CRYO-EM STRUCTURE; VALIDATION; SPIKE; REPLICATION; INFECTION; LIBRARIES; TOOLS; MODEL;

D O I：

10.1016/j.celrep.2022.111528

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented num-ber of mutations, raise serious concerns due to the reduced efficacy of current vaccines and resistance to therapeutic antibodies. Here, we report the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein. NA8 inter-acts with a highly conserved region and has a breadth of neutralization with picomolar potency against the Beta variant and the Omicron BA.1 and BA.2 sublineages and nanomolar potency against BA.2.12.1 and BA.4. Combination of NA8 and NE12 retains potent neutralizing activity against the major SARS-CoV-2 var-iants of concern. Cryo-EM analysis provides the structural basis for the broad and complementary neutral-izing activity of these two antibodies. We confirm the in vivo protective and therapeutic efficacies of NA8 and NE12 in the hamster model. These results show that broad and potent human antibodies can overcome the continuous immune escape of evolving SARS-CoV-2 variants.

引用

页数：25

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