![]() In particular, the receptor-binding domain (RBD) of the spike protein has undergone more than 15 amino acid substitutions, altering both the transmissibility and its recognition by the immune system 2, 3. Omicron variant is characterized by significant mutation in its spike (S) protein, which is a major target of vaccines. Among these, the Omicron variant (B.1.1.529) emerged rapidly since November 2021, leading to subsequent waves of infections worldwide 1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing coronavirus disease 2019 (COVID-19), continues to undergo evolutionary changes, resulting in the emergency of new variants of concern (VOCs). 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. 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. These bnAbs target four antigenic sites within the RBD. 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 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. We observed that the long-interval group exhibited higher and broader serologic antibody responses. 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. 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. Some individuals received three doses of ZF2001, with a one-month interval between each dose, due to urgent clinical requirements. This vaccine has been administered using different dosing intervals in real-world setting. Previously, we developed a protein subunit COVID-19 vaccine called ZF2001, based on the dimeric receptor-binding domain (RBD). ![]() However, the vaccine-elicited antibodies have reduced efficiency against the highly mutated Omicron sub-variants. Vaccination with different vaccines has been implemented globally to counter the continuous COVID-19 pandemic.
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