Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine

Guo，Shuxin1,2; Zheng，Yuxuan3; Gao，Zhengrong4,5; Duan，Minrun6; Liu，Sheng7; Du，Pan8; Xu，Xiao Yu8; Xu，Kun9; Zhao，Xin3; Chai，Yan3; Wang，Peiyi7; Zhao，Qi10; Gao，George F.2,3,9; Dai，Lianpan3

2023-12-01

10.1038/s41421-023-00585-5

Cell Discovery   Impact Factor & Quartile

2056-5968

2056-5968

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.

SCI

English

Others

National Natural Science Foundation of China-Yunnan Joint Fund[81991494];National Natural Science Foundation of China-Yunnan Joint Fund[82041048];National Natural Science Foundation of China-Yunnan Joint Fund[82122031];Bill and Melinda Gates Foundation[INV-027420];Institute of Microelectronics of the Chinese Academy of Sciences[YSBR-010];

Cell Biology

Cell Biology

WOS:001040456600003

SPRINGERNATURE

2-s2.0-85167472331

Scopus

1.Faculty of Health Sciences,University of Macau,SAR,Macao
2.Savaid Medical School,University of Chinese Academy of Sciences,Beijing,China
3.CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China
4.Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong,China
5.Shenzhen Children’s Hospital,Shenzhen,Guangdong,China
6.School of Life Sciences,Yunnan University,Kunming,Yunnan,China
7.Department of Biology,Cryo-EM Center,Southern University of Science and Technology,Shenzhen,Guangdong,China
8.Vazyme Biotech,Nanjing,Jiangsu,China
9.Research Network of Immunity and Health (RNIH),Beijing Institutes of Life Science,Chinese Academy of Sciences,Beijing,China
10.MoE Frontiers Science Center for Precision Oncology,Faculty of Health Sciences,University of Macau,SAR,Macao

Guo，Shuxin,Zheng，Yuxuan,Gao，Zhengrong,et al. Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine[J]. Cell Discovery,2023,9(1).

Guo，Shuxin.,Zheng，Yuxuan.,Gao，Zhengrong.,Duan，Minrun.,Liu，Sheng.,...&Dai，Lianpan.(2023).Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine.Cell Discovery,9(1).

Guo，Shuxin,et al."Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine".Cell Discovery 9.1(2023).