Proteome‐minimized outer membrane vesicles from Escherichia coli as a generalized vaccine platform

Journal of Extracellular Vesicles

卷:10

Assunta Gagliardi¹  Martina Grigolato¹  Luca Frattini¹  Michele Tomasi¹  Enrico König¹  Francesca Zerbini¹  Samine J. Isaac¹  Carmela Irene¹  Ilaria Zanella¹  Riccardo Corbellari¹  Elena Caproni¹  Guido Grandi¹  Luca Bini²  Fabiola Giusti³  Ilaria Ferlenghi³  Yaqoub Ashhab⁴  Alberto Grandi⁵  Silvia Valensin⁵  Laura Fantappiè⁵ 

[1] Department of Cellular, Computational and Integrative Biology (CIBIO) Laboratory of Synthetic and Structural Vaccinology University of Trento Trento Italy;

[2] Department of Life Sciences Functional Proteomics Laboratories University of Siena Siena Italy;

[3] GlaxoSmithKline Vaccines Siena Italy;

[4] Palestine‐Korea Biotechnology Center Palestine Polytechnic University Hebron Palestine;

[5] Toscana Life Sciences Foundation Siena Italy;

关键词: cancer;    infectious diseases;    outer membrane vesicles (OMVs);    synthetic biology;    vaccines;   

DOI  :  10.1002/jev2.12066

来源: DOAJ

【 摘 要 】

Abstract 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 (OMVsΔ60) 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, OMVsΔ60 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.

【 授权许可】

Unknown