Engineering probiotic-derived outer membrane vesicles as functional vaccine carriers to enhance immunity against SARS-CoV-2
Jing Wo,
Zhao-Yong Lv,
Jia-Nan Sun,
Hao Tang,
Nan Qi,
Bang-Ce Ye
Affiliations
Jing Wo
Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014 Zhejiang, China
Zhao-Yong Lv
Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014 Zhejiang, China
Jia-Nan Sun
Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014 Zhejiang, China
Hao Tang
Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014 Zhejiang, China
Nan Qi
Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014 Zhejiang, China
Bang-Ce Ye
Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014 Zhejiang, China; Lab of Biosystem and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Corresponding author
Summary: Because of the continued emergence of SARS-CoV-2 variants, there has been considerable interest in how to display multivalent antigens efficiently. Bacterial outer membrane vesicles (OMVs) can serve as an attractive vaccine delivery system because of their self-adjuvant properties and the ability to be decorated with antigens. Here we set up a bivalent antigen display platform based on engineered OMVs using mCherry and GFP and demonstrated that two different antigens of SARS-CoV-2 could be presented simultaneously in the lumen and on the surface of OMVs. Comparing immunogenicity, ClyA-NG06 fusion and the receptor-binding domain (RBD) of the spike protein in the OMV lumen elicited a stronger humoral response in mice than OMVs presenting either the ClyA-NG06 fusion or RBD alone. Taken together, we provided an efficient approach to display SARS-CoV-2 antigens in the lumen and on the surface of the same OMV and highlighted the potential of OMVs as general multi-antigen carriers.
