Research by CPL Leading Scientists among China's top 10 advances in life sciences in 2022

2023-01-22

On Jan 18, the China Association for Science and Technology (CAST) released the country's 10 most significant advances in the field of life sciences in 2022. The work on “the immune evasion of SARS-CoV-2 mutants” by Xiaoliang Sunney Xie and Yunlong Cao’s team and that on “the precision treatment solution of ischemic cerebrovascular diseases” by Yongjun Wang’s team were included in the list.

The immune evasion of SARS-CoV-2 mutants

The SARS-CoV-2 Omicron strain keeps mutating, causing infection waves around the globe. Deciphering how SARS-CoV-2 mutants evade humoral immunity is instrumental to vaccine development and the prevention and control of COVID-19 pandemic.

The project led by Xie and Cao’s team at CPL, in collaboration with Xiangxi Wang’s team from Institute of Biophysics at Chinese Academy of Sciences and Youchun Wang’s team from National Institutes for Food and Drug Control (NIFDC), was the first to report on the antibody escape mechanisms of Omicron and its subvariants.

They were the world’s first to reveal the structure and infection characteristics of various mutants, while profiling the epitopes and escaping mutations of SARS-CoV-2 neutralizing antibodies. It was found that mutations carried by Omicron BA.1 can escape the neutralizing antibodies (NAbs) induced by wild-type SARS-CoV-2 vaccination/infection and BA.4/BA.5 can escape NAbs induced by BA.1 infection and vaccination, suggesting that it is unlikely to achieve herd immunity through Omicron infection. These findings are highly timely and relevant for global pandemic prevention and control and provide a theoretical basis for the research and development of new broad-spectrum COVID-19 vaccines and antibody drugs.

Related studies have been published in Nature, Cell and Cell Host & Microbe (Nature, 608:593-6021; Nature, 602:657-6632; Nature, 603:919-9253; Cell, 185(5):860-8714；Cell Host & Microbe, 30(11): 1527-1539.e55).

Spike protein structure and immune evasion mechanisms of Omicron BA.1

Related publications:

1          Cao, Y. et al. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature 608, 593-602, doi:10.1038/s41586-022-04980-y (2022).

2          Cao, Y. et al. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature 602, 657-663, doi:10.1038/s41586-021-04385-3 (2022).

3          Wang, K. et al. Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants. Nature 603, 919-925, doi:10.1038/s41586-022-04466-x (2022).

4          Cui, Z. et al. Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron. Cell 185, 860-871.e813, doi:10.1016/j.cell.2022.01.019 (2022).

5          Cao, Y. et al. Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75. Cell Host Microbe 30, 1527-1539.e1525, doi:10.1016/j.chom.2022.09.018(2022).

 

Precision treatment solution of ischemic cerebrovascular diseases

High recurrence rate is a global challenge for the secondary prevention of ischemic cerebrovascular diseases. Although aspirin as a singular antiplatelet therapy has been recommended by national guidelines, it has limited efficacy to prevent recurrence. Some clinical trials of combined antiplatelet therapy with other drugs (dual antiplatelet therapy) were launch around the world, however, all of them failed due to ineffectiveness or increased risk of serious bleeding. Therefore, combined antiplatelet therapy was once prohibited to use in patients with ischemic cerebrovascular diseases by the international guidelines.

Yongjun Wang and his team, who were from Beijing Tiantan Hospital, Capital Medical University, proposed for the first time in the world a new treatment solution that effectively reduced the rate of recurrence by a short term, dual-channel, dual-effect combination use of aspirin and clopidogrel without increasing the risk of serious bleeding. This dual antiplatelet therapy solution has been endorsed by international guidelines and widely implemented in the whole world. Based on this regimen, he found that ABCB1, CYP2C19 and F2R, three key genes in the absorption and metabolism pathway of clopidogrel, all significantly affect the efficacy of this dual antiplatelet solution. For those patients who carried the loss-function allele of CYP2C19, he proposed a "gene bypass" solution that clopidogrel replaced by ticagrelor and testified its efficacy of reducing the recurrence risk by 23% without increasing serious bleeding. It was commented as opening a new era of gene-guided therapy for cerebrovascular diseases by the New England Journal of Medicine and a second CHANCE for genotype-guided dual antiplatelet therapy.

These findings were published in the New England Journal of Medicine (N Engl J Med 2021,385(27): 2520-2530).

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA