Open AccessProteome‐minimized outer membrane vesicles from Escherichia coli as a generalized vaccine platform
Author(s) -
Zanella Ilaria,
König Enrico,
Tomasi Michele,
Gagliardi Assunta,
Frattini Luca,
Fantappiè Laura,
Irene Carmela,
Zerbini Francesca,
Caproni Elena,
Isaac Samine J.,
Grigolato Martina,
Corbellari Riccardo,
Valensin Silvia,
Ferlenghi Ilaria,
Giusti Fabiola,
Bini Luca,
Ashhab Yaqoub,
Grandi Alberto,
Grandi Guido
Publication year - 2021
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1002/jev2.12066
Subject(s) - epitope , escherichia coli , heterologous , antigen , bacterial outer membrane , biology , vesicle , recombinant dna , microbiology and biotechnology , proteome , membrane protein , chemistry , biochemistry , membrane , immunology , gene
Because of their potent adjuvanticity, ease of manipulation and simplicity of production Gram‐negative Outer Membrane Vesicles OMVs have the potential to become a highly effective vaccine platform. However, some optimization is required, including the reduction of the number of endogenous proteins, the increase of the loading capacity with respect to heterologous antigens, the enhancement of productivity in terms of number of vesicles per culture volume. In this work we describe the use of Synthetic Biology to create Escherichia coli BL21(DE3)Δ60, a strain releasing OMVs (OMVs Δ60 ) deprived of 59 endogenous proteins. The strain produces large quantities of vesicles (> 40 mg/L under laboratory conditions), which can accommodate recombinant proteins to a level ranging from 5% to 30% of total OMV proteins. Moreover, also thanks to the absence of immune responses toward the inactivated endogenous proteins, OMVs Δ60 decorated with heterologous antigens/epitopes elicit elevated antigens/epitopes‐specific antibody titers and high frequencies of epitope‐specific IFN‐γ‐producing CD8 + T cells. Altogether, we believe that E. coli BL21(DE3)Δ60 have the potential to become a workhorse factory for novel OMV‐based vaccines.