SARS-CoV-2 Omicron Variants Reduce Antibody Neutralization and Acquire Usage of Mouse ACE2

Wang, Ruoke1,2; Zhang, Qi1; Zhang, Rui1; Aw, Zhen Qin3,4,5; Chen, Peng1; Wong, Yi Hao3,4,5; Hong, Junxian1; Ju, Bin6,7; Shi, Xuanling1; Ding, Qiang8,9; Zhang, Zheng6,7; Chu, Justin Jang Hann3,4,5; Zhang, Linqi1,10,11

2022-06-17

10.3389/fimmu.2022.854952

Frontiers in Immunology   Impact Factor & Quartile

1664-3224

Striking number of mutations found in the spike protein of recently emerged SARS-CoV-2 Omicron subvariants BA.1, BA.2, BA.3 and BA.4/5 has raised serious concerns regarding the escape from current antibody therapies and vaccine protection. Here, we conducted comprehensive analysis on the extent of two major Omicron lineages BA.1/BA.1.1 and BA.2 to escape neutralization from the therapeutic antibodies approved by the regulatory authorities and convalescent plasma from SARS-CoV-2 patients infected during initial wave of pandemic in early 2020. We showed that Omicron BA.1/BA.1.1 were the most resistant in both magnitude and breadth against antibodies and convalescent plasma, followed by Beta, BA.2, Gamma, Delta and Alpha. While the majority of therapeutic antibodies lost binding and neutralization to Omicron variants, BRII combo (BRII-196 + BRII-198), S309, and AZ combo (COV2-2196 + COV2-2130) maintained neutralization despite of reduction due to either conserved epitope or combinational effect between the two designated antibodies. A single intraperitoneal injection of BRII combo as a prophylactic treatment protected animals from Omicron infection. Treated animals manifested normal body weight, survived infection up to 14 days, undetectable levels of infectious viruses in the lungs, and reduced lung pathology compared to the controls. Analyzing ACE2 from diverse host species showed that Omicron variants acquired ability to use mouse ACE2 for entry. These results demonstrate major antigenic shifts and potentially broadening the host range of two major Omicron lineages BA.1/BA.1.1 and BA.2, posing serious challenges to current antibody therapies and vaccine protection as well as increasing danger of spillover into the wildlife.

Omicron variant antibody neutralization ACE2 orthologues SARS-CoV-2 infection (COVID-19) plasma neutralization

SCI

English

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National Key Plan for Scientific Research and Development of China["2020YFC0848800","2020YFC0849900","2021YFC0864500","2020YFC0861200"] ; National Natural Science Foundation[92169205,81530065,81661128042,9216920007,32000661] ; Beijing Municipal Science and Technology Commission["D171100000517001","D171100000517003","Z201100005420019"] ; Science and Technology Innovation Committee of Shenzhen Municipality[202002073000002,"JSGG20200807171401008"] ; Beijing Advanced Innovation Center for Structural Biology, Tsinghua University Scientific Research Program[20201080053,"2020Z99CFG004"] ; National Science Fund for Distinguished Young Scholars[82025022] ; Singapore National Medical Research Council Centre Grant Program[CGAug16M009] ; Singapore NMRC Centre Grant Program -Diabetes, Tuberculosis and Neuroscience[CGAug16M009] ; Singapore Ministry of Health[MOH-COVID19RF2-0001] ; [NUHSRO/2020/066/NUSMedCovid/01/BSL3] ; [NUHSRO/2020/050/RO5+5/NUHS-COVID/4]

Immunology

Immunology

WOS:000819458300001

FRONTIERS MEDIA SA

Web of Science

1.Tsinghua Univ, Ctr Global Hlth & Infect Dis, Comprehens AIDS Res Ctr, Sch Med,Dept Basic Med Sci, Beijing, Peoples R China
2.Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China
3.Natl Univ Singapore, Yong Loo Lin Sch Med, Biosafety Level 3 Core Facil, Singapore, Singapore
4.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Lab Mol RNA Virol & Antiviral Strategies, Singapore, Singapore
5.Natl Univ Singapore, Yong Loo Lin Sch Med, Infect Dis Translat Res Programme, Singapore, Singapore
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Inst Hepatol,Natl Clin Res Ctr Infect Dis,Sch Med, Shenzhen, Peoples R China
7.Southern Univ Sci & Technol, Affiliated Hosp 2, Sch Med, Shenzhen, Peoples R China
8.Tsinghua Univ, Ctr Infect Dis Res, Sch Med, Beijing, Peoples R China
9.Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China
10.Tsinghua Univ, Inst Biopharmaceut & Hlth Engn, Tsinghua Shenzhen Int Grad Sch, Shenzhen, Peoples R China
11.Shenzhen Bay Lab, Inst Biomed Hlth Technol & Engn, Shenzhen, Peoples R China

Wang, Ruoke,Zhang, Qi,Zhang, Rui,et al. SARS-CoV-2 Omicron Variants Reduce Antibody Neutralization and Acquire Usage of Mouse ACE2[J]. Frontiers in Immunology,2022,13.

Wang, Ruoke.,Zhang, Qi.,Zhang, Rui.,Aw, Zhen Qin.,Chen, Peng.,...&Zhang, Linqi.(2022).SARS-CoV-2 Omicron Variants Reduce Antibody Neutralization and Acquire Usage of Mouse ACE2.Frontiers in Immunology,13.

Wang, Ruoke,et al."SARS-CoV-2 Omicron Variants Reduce Antibody Neutralization and Acquire Usage of Mouse ACE2".Frontiers in Immunology 13(2022).