Antibody-mediated immunity induced by engineered Escherichia coli OMVs carrying heterologous antigens in their lumen

Autor:	Immaculada Margarit, Guido Grandi, Filippo Carboni, Giuliano Bensi, Emiliano Chiarot, Olivier Jousson, Laura Fantappiè, Micaela de Santis
Jazyk:	angličtina
Rok vydání:	2014
Předmět:	Group B Streptococcus Histology medicine.disease_cause law.invention Microbiology 03 medical and health sciences outer membrane vesicles vaccines heterologous antigens periplasmic expression Group A Streptococcus Chlamydia trachomatis Antigen law medicine Secretion Original Research Article lcsh:QH573-671 Escherichia coli 030304 developmental biology 0303 health sciences biology 030306 microbiology lcsh:Cytology Immunogenicity Cell Biology Periplasmic space 3. Good health biology.protein Recombinant DNA Antibody Bacterial outer membrane
Zdroj:	Journal of Extracellular Vesicles Journal of Extracellular Vesicles, Vol 3, Iss 0, Pp 1-14 (2014) Journal of Extracellular Vesicles; Vol 3 (2014) incl supplements
ISSN:	2001-3078
Popis:	Background : Outer membrane vesicles (OMVs) from Gram-negative bacteria are gaining increasing attention as vaccine platform for their built-in adjuvanticity and for their potential use as carriers of heterologous antigens. These 2 properties offer the opportunity to make highly effective, easy to produce multi-valent vaccines. OMVs can be loaded with foreign antigens by targeting protein expression either to the outer membrane or to the periplasm of the OMV-producing strain. Periplasmic expression is simple and relatively efficient but leads to the accumulation of recombinant antigens in the lumen of OMVs and the ability of OMVs carrying internalized antigens to induce antigen-specific antibody responses has been only marginally investigated and is considered to be sub-optimal. Methods : We have systematically analyzed in qualitative and quantitative terms antibody responses induced by OMVs carrying different heterologous antigens in their lumen. Group A Streptococcus (GAS) Slo, SpyCEP, Spy0269 and Group B Streptococcus (GBS) SAM_1372 were fused to the OmpA leader sequence for secretion and expressed in Escherichia coli . OMVs from the recombinant strains were purified and tested for immunogenicity and protective activity. Results : All proteins were incorporated into the OMVs lumen in their native conformation. Upon mice immunization, OMVs induced high functional antibody titers against the recombinant proteins. Furthermore, immunization with Slo-OMVs and SpyCEP-OMVs protected mice against GAS lethal challenge. Conclusions : The efficiency of antigen delivery to the vesicular lumen via periplasmic expression, and the surprisingly high immunogenicity and protective activity of OMVs carrying internalized recombinant antigens further strengthens the potential of OMVs as vaccine platform. Keywords: outer membrane vesicles; vaccines; heterologous antigens; periplasmic expression; Group A Streptococcus; Group B Streptococcus (Published: 11 August 2014) Citation: Journal of Extracellular Vesicles 2014, 3 : 24015 - http://dx.doi.org/10.3402/jev.v3.24015
Databáze:	OpenAIRE
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