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
Svennerholm, Kristina,1981Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för anestesiologi och intensivvård,Institute of Clinical Sciences, Department of Anesthesiology and Intensive care(Swepub:gu)xskrix
(författare)
Crescitelli, Rossella,1985Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xcrero
(författare)
Lässer, Cecilia,1981Gothenburg University,Göteborgs universitet,Institutionen för medicin,Krefting Research Centre,Institute of Medicine(Swepub:gu)xlasce
(författare)
Gribonika, Inta,1992Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xgribi
(författare)
Andersson, MickaelGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
(författare)
Boström, JonasGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
(författare)
Alalam, Hanna,1993Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xalalh
(författare)
Harandi, Ali M,1968Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xharal
(författare)
Farewell, Anne,1961Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xfaran
(författare)
Lötvall, Jan,1956Gothenburg University,Göteborgs universitet,Institutionen för medicin,Krefting Research Centre,Institute of Medicine(Swepub:gu)xlotja
(författare)
Göteborgs universitetInstitutionen för medicin
(creator_code:org_t)
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Ingår i:Journal of Nanobiotechnology: Springer Science and Business Media LLC21:11477-3155