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-Structure paper
タイトル | Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine. |
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ジャーナル・号・ページ | Cell Discov, Vol. 9, Issue 1, Page 79, Year 2023 |
掲載日 | 2023年7月28日 |
著者 | Shuxin Guo / Yuxuan Zheng / Zhengrong Gao / Minrun Duan / Sheng Liu / Pan Du / XiaoYu Xu / Kun Xu / Xin Zhao / Yan Chai / Peiyi Wang / Qi Zhao / George F Gao / Lianpan Dai / |
PubMed 要旨 | Vaccination with different vaccines has been implemented globally to counter the continuous COVID-19 pandemic. However, the vaccine-elicited antibodies have reduced efficiency against the highly ...Vaccination with different vaccines has been implemented globally to counter the continuous COVID-19 pandemic. However, the vaccine-elicited antibodies have reduced efficiency against the highly mutated Omicron sub-variants. Previously, we developed a protein subunit COVID-19 vaccine called ZF2001, based on the dimeric receptor-binding domain (RBD). This vaccine has been administered using different dosing intervals in real-world setting. Some individuals received three doses of ZF2001, with a one-month interval between each dose, due to urgent clinical requirements. Others had an extended dosing interval of up to five months between the second and third dose, a standard vaccination regimen for the protein subunit vaccine against hepatitis B. In this study, we profile B cell responses in individuals who received three doses of ZF2001, and compared those with long or short dosing intervals. We observed that the long-interval group exhibited higher and broader serologic antibody responses. These responses were associated with the increased size and evolution of vaccine-elicited B-cell receptor repertoires, characterized by the elevation of expanded clonotypes and somatic hypermutations. Both groups of individuals generated substantial amounts of broadly neutralizing antibodies (bnAbs) against various SARS-CoV-2 variants, including Omicron sub-variants such as XBB. These bnAbs target four antigenic sites within the RBD. To determine the vulnerable site of SARS-CoV-2, we employed cryo-electron microscopy to identify the epitopes of highly potent bnAbs that targeted two major sites. Our findings provide immunological insights into the B cell responses elicited by RBD-based vaccine, and suggest that a vaccination regimen of prolonging time interval should be used in practice. |
リンク | Cell Discov / PubMed:37507370 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.34 - 2.85 Å |
構造データ | EMDB-34928, PDB-8hp9: EMDB-34931, PDB-8hpf: EMDB-34940, PDB-8hpq: EMDB-34944, PDB-8hpu: EMDB-34945, PDB-8hpv: EMDB-34946, PDB-8hq7: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / SARS-CoV-2 / Omicron BA.2 S-trimer / Cryo-EM structure / fab / IMMUNE SYSTEM-VIRAL PROTEIN complex / Omicron BA.2 RBD / Omicron BA.4 S-trimer / Omicron BA.4 RBD / Omicron Prototype S-trimer / Omicron Prototype RBD |