ArticleNature immunology2024
The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis.
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Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Molecular mechanisms of immune evasion by host protein glycosylation of a bacterial immunogen used in nucleic acid vaccines.The Journal of biological chemistry · 2026Article
- Immunological and pathological roles of Siglecs: a molecular review.Frontiers in immunology · 2026Review
- Applications of Pseudoviruses Bearing Glycoproteins of SARS-CoV-2 and Influenza Virus.Advances in experimental medicine and biology · 2026Review
- The role of SIGLEC9 in immunosuppression and prognosis in cervical cancer.Clinics (Sao Paulo, Brazil) · 2025Article
- Increase of Inhibitory Siglec receptors on T cells mitigates severe immune reactions during acute viral infections.PNAS nexus · 2025Article
- Targeting heptad repeats and fusion peptide: nanoparticle vaccine elicits mucosal immune response against SARS-CoV-2 variants.Journal of nanobiotechnology · 2025Article
- Intrinsic immunogenicity is a major determinant of type-specific responses in SARS-CoV-2 infections.Nature immunology · 2025Article
- The Compensatory Effect of S375F on S371F Is Vital for Maintaining the Infectivity of SARS-CoV-2 Omicron Variants.Journal of medical virology · 2025Article
- Advances in the structure-based design of protein vaccines for respiratory infectious diseases.Computational and structural biotechnology journal · 2025Review
- Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic.Nature microbiology · 2025Article
- Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants.Nature communications · 2024Article
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Authors and funding
38 authors at 5 institutions in 1 country.
Xin He *Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.ORCID http://orcid.org/0000-0002-2131-2092
Xiantao Zhang *Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Bolin Wu *Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Jieyi Deng *Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Yongli Zhang *Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Airu Zhu *Guangzhou Laboratory, Bio-island, Guangzhou, China.
Yaochang YuanInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Yingtong LinInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Achun ChenInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Jinzhu FengInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Xiumei WangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Shijian WuInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Yingying LiuInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Jie LiuInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Yalin WangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Rong LiInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Chaofeng LiangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Quyu YuanInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Yu LiangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Qiannan FangGuangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guanzhou, China.
Zhihui XiGuangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guanzhou, China.
Wenjie LiInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Liting LiangQianyang Biomedical Research Institute, Guangzhou, China.
Zhenglai ZhangGuangzhou Laboratory, Bio-island, Guangzhou, China.
Hui TangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Yi PengInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Changwen KeGuangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
Xiancai MaGuangzhou Laboratory, Bio-island, Guangzhou, China.ORCID http://orcid.org/0000-0002-4934-4221
Weibin CaiLaboratory Animal Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.ORCID http://orcid.org/0000-0003-0934-4507
Ting PanInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Bingfeng LiuInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Kai DengInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.ORCID http://orcid.org/0000-0002-9973-8130
Jun ChenInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.ORCID http://orcid.org/0000-0001-8051-5503
Jincun ZhaoGuangzhou Laboratory, Bio-island, Guangzhou, China. zhaojincun@gird.cn.ORCID http://orcid.org/0000-0003-2515-5589
Xuepeng WeiGuangzhou Laboratory, Bio-island, Guangzhou, China. wei_xuepeng@gzlab.ac.cn.ORCID http://orcid.org/0000-0002-6514-7076
Ran ChenInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. chenran7@mail.sysu.edu.cn.ORCID http://orcid.org/0009-0003-0668-9136
Yiwen ZhangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. zhangyw57@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0002-5232-0335
Hui ZhangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. zhangh92@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0003-3620-610X
Sun Yat-sen University · CNGuangzhou Regenerative Medicine and Health Guangdong Laboratory · CNFirst Affiliated Hospital of Guangzhou Medical University · CNGuangdong Academy of Medical Sciences · CNGuangdong Provincial Center for Disease Control and Prevention · CN
Funding
National Natural Science Foundation of China (National Science Foundation of China) 32100743National Natural Science Foundation of China (National Science Foundation of China) 92369205
Abstract
The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.
Indexed as
COVID-19SARS-CoV-2AnimalsAntibodies, NeutralizingAntibodies, ViralAntigens, CDMacaca mulattaMacrophagesMiceNanovaccinesPhagocytosisRabbitsSialic Acid Binding Immunoglobulin-like LectinsAntibodies, NeutralizingAntibodies, ViralAntigens, CDNanovaccinesSialic Acid Binding Immunoglobulin-like LectinsSIGLEC9 protein, humansiglec-9 protein, mouse
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