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TitleDosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine.
Journal, issue, pagesCell Discov, Vol. 9, Issue 1, Page 79, Year 2023
Publish dateJul 28, 2023
AuthorsShuxin 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 AbstractVaccination 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.
External linksCell Discov / PubMed:37507370 / PubMed Central
MethodsEM (single particle)
Resolution2.34 - 2.85 Å
Structure data

EMDB-34928, PDB-8hp9:
Cryo-EM structure of SARS-CoV-2 Omicron BA.2 S-trimer in complex with fab L4.65 and L5.34
Method: EM (single particle) / Resolution: 2.75 Å

EMDB-34931, PDB-8hpf:
Cryo-EM structure of SARS-CoV-2 Omicron BA.2 RBD in complex with fab L4.65 and L5.34
Method: EM (single particle) / Resolution: 2.34 Å

EMDB-34940, PDB-8hpq:
Cryo-EM structure of SARS-CoV-2 Omicron BA.4 S-trimer in complex with fab L4.65 and L5.34
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-34944, PDB-8hpu:
Cryo-EM structure of SARS-CoV-2 Omicron BA.4 RBD in complex with fab L4.65 and L5.34
Method: EM (single particle) / Resolution: 2.56 Å

EMDB-34945, PDB-8hpv:
Cryo-EM structure of SARS-CoV-2 Omicron Prototype S-trimer in complex with fab L4.65 and L5.34
Method: EM (single particle) / Resolution: 2.65 Å

EMDB-34946, PDB-8hq7:
Cryo-EM structure of SARS-CoV-2 Omicron Prototype RBD in complex with fab L4.65 and L5.34
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsIMMUNE 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

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