Detoxified synthetic bacterial membrane vesicles as a vaccine platform against bacteria and SARS-CoV-2

Journal of Nanobiotechnology

Research

Kristina Svennerholm¹  Anne Farewell²  Mickael Andersson²  Jonas Boström²  Hanna Alalam²  Inta Gribonika³  Ali M Harandi⁴  Rossella Crescitelli⁵  Jan Lötvall⁶  Kyong-Su Park⁶  Cecilia Lässer⁶ 

[1] Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Department of Chemistry and Molecular Biology, Centre for Antibiotic Resistance, University of Gothenburg, Gothenburg, Sweden;Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;BC Children’s Hospital Research Institute, Vaccine Evaluation Center, University of British Columbia, Columbia, Canada;Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Department of Surgery, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden;Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden;Krefting Research Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;

关键词: Synthetic bacterial vesicles;    Outer membrane vesicles;    Vaccine;    Pulmonary inflammation;    Sepsis;    COVID-19;   

DOI  :  10.1186/s12951-023-01928-w

 received in 2023-01-27, accepted in 2023-05-13,  发布年份 2023

来源: Springer

【 摘 要 】

The development of vaccines based on outer membrane vesicles (OMV) that naturally bud off from bacteria is an evolving field in infectious diseases. However, the inherent inflammatory nature of OMV limits their use as human vaccines. This study employed an engineered vesicle technology to develop synthetic bacterial vesicles (SyBV) that activate the immune system without the severe immunotoxicity of OMV. SyBV were generated from bacterial membranes through treatment with detergent and ionic stress. SyBV induced less inflammatory responses in macrophages and in mice compared to natural OMV. Immunization with SyBV or OMV induced comparable antigen-specific adaptive immunity. Specifically, immunization with Pseudomonas aeruginosa-derived SyBV protected mice against bacterial challenge, and this was accompanied by significant reduction in lung cell infiltration and inflammatory cytokines. Further, immunization with Escherichia coli-derived SyBV protected mice against E. coli sepsis, comparable to OMV-immunized group. The protective activity of SyBV was driven by the stimulation of B-cell and T-cell immunity. Also, SyBV were engineered to display the SARS-CoV-2 S1 protein on their surface, and these vesicles induced specific S1 protein antibody and T-cell responses. Collectively, these results demonstrate that SyBV may be a safe and efficient vaccine platform for the prevention of bacterial and viral infections.

【 授权许可】

CC BY   
© The Author(s) 2023

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