Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development

Zhou, Yuchen1; Qu, Jing2; Sun, Xiaomeng1; Yue, Zhuo1; Liu, Yingzi3; Zhao, Keli3,4; Yang, Fan1; Feng, Jie1; Pan, Xiaolei1; Jin, Yongxin1; Cheng, Zhihui1; Yang, Liang5; Ha, Un-Hwan6; Wu, Weihui1; Li, Liang5; Bai, Fang1

2023-02-21

10.3389/fimmu.2023.1129705

Frontiers in Immunology   Impact Factor & Quartile

1664-3224

COVID-19 pandemic continues to spread throughout the world with an urgent demand for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a bacterial vector COVID-19 vaccine (aPA-RBD) that carries the gene for the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Live-attenuated strains of Pseudomonas aeruginosa (aPA) were constructed which express the recombinant RBD and effectively deliver RBD protein into various antigen presenting cells through bacterial type 3 secretion system (T3SS) in vitro. In mice, two-dose of intranasal aPA-RBD vaccinations elicited the development of RBD-specific serum IgG and IgM. Importantly, the sera from the immunized mice were able to neutralize host cell infections by SARS-CoV-2 pseudovirus as well as the authentic virus variants potently. T-cell responses of immunized mice were assessed by enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICS) assays. aPA-RBD vaccinations can elicit RBD-specific CD4(+)and CD8(+)T cell responses. T3SS-based RBD intracellular delivery heightens the efficiency of antigen presentation and enables the aPA-RBD vaccine to elicit CD8(+)T cell response. Thus, aPA vector has the potential as an inexpensive, readily manufactured, and respiratory tract vaccination route vaccine platform for other pathogens

SARS-CoV-2 vaccine Pseudomonas aeruginosa live-attenuated type 3 secretion system (T3SS) anti-virus immunity

SCI

English

Corresponding

National Natural Science Foundation of China["31870130","31970680","31970179","32170199","82061148018"] ; National Key Research and Development Project of China["2021YFE0201300","2021YFE0101700"] ; National Research Foundation of Korea[NRF-2020K2A9A2A11102267]

Immunology

Immunology

WOS:000943461400001

FRONTIERS MEDIA SA

Web of Science

1.Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Mol Microbiol, Tianjin, Peoples R China
2.Shenzhen Ctr Dis Control & Prevent, Dept Pathogen Biol, Shenzhen, Peoples R China
3.Peking Univ, Shenzhen Hosp, Intervent & Cell Therapy Ctr, Shenzhen, Peoples R China
4.Peking Univ, Hong Kong Univ Sci, Technol Med Ctr, Shenzhen, Peoples R China
5.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Shenzhen, Peoples R China
6.Korea Univ, Dept Biotechnol & Bioinformat, Sejong, South Korea

Zhou, Yuchen,Qu, Jing,Sun, Xiaomeng,et al. Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development[J]. Frontiers in Immunology,2023,14.

Zhou, Yuchen.,Qu, Jing.,Sun, Xiaomeng.,Yue, Zhuo.,Liu, Yingzi.,...&Bai, Fang.(2023).Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development.Frontiers in Immunology,14.

Zhou, Yuchen,et al."Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development".Frontiers in Immunology 14(2023).