A trimeric RBD protein as a booster vaccine enhanced the humoral response and broad neutralization against SARS-CoV-2 in mice
10.3760/cma.j.cn112309-20220817-00265
- VernacularTitle:新型冠状病毒重组RBD重复串联三聚体蛋白疫苗作为加强针可在小鼠中诱导较强的免疫应答和交叉中和反应
- Author:
Xiujing HONG
1
;
Yangyang HU
;
Kangli CAO
;
Longfei DING
;
Nan GAO
;
Xiangwei WANG
;
Chen ZHAO
;
Xiaoyan ZHANG
;
Jianqing XU
Author Information
1. 复旦大学生物医学研究院，上海 200032
- Keywords:
SARS-CoV-2;
Protein vaccine;
Humoral immunity;
Receptor binding domain;
Variants
- From:
Chinese Journal of Microbiology and Immunology
2022;42(11):837-844
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the efficacy of a SARS-CoV-2 recombinant protein vaccine as a booster dose.Methods:A new immunogen, namely RBD-sc-trimer, was designed by tandem repeating of single receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein to mimic the trimeric form of RBD presented by the virus. The RBD-sc-trimer protein was expressed as a His-tagged fusion protein using a baculovirus expression system and purified by nickel affinity column. The purified protein was identified by Western blot. Its in vitro binding activity to human angiotensin converting enzyme 2 (hACE2) was analyzed by ELISA. The immunogenicity of RBD-sc-trimer as well as RBD proteins of other forms including RBD dimer (RBD-Fc), RBD monomer (RBD) and S protein trimer (S trimer) as a booster dose was evaluated in BALB/c mice. Results:In terms of both binding and neutralizing antibodies against SARS-CoV-2, RBD-sc-trimer showed an immunogenicity that was superior to that of RBD-Fc and RBD and close to the level of S trimer. The antibody response induced by RBD-sc-trimer was characterized as Th1-biased. Moreover, it displayed a stronger cross-neutralization activity against SARS-CoV-2 Beta, Delta and Omicron variants. The titer of neutralizing antibody against Omicron induced by RBD-sc-trimer only decreased by 9.1 folds relative to the prototype strain, while the antibody response induced by RBD-Fc and S trimer decreased by 68.4 and 70.8 folds, respectively.Conclusions:The recombinant protein, RBD-sc-trimer, which was capable of eliciting stronger humoral response in mice as a booster dose and showed the superiority in raising cross-reactive antibodies against SARS-CoV-2 variants over non-trimeric RBD forms, should be considered as an optimal immunogen for the development of more effective SARS-CoV-2 vaccines.
