title: Homologous prime boosting based on intranasal delivery of non-pathogenic invasive Escherichia coli expressing MPT64, decreases Mycobacterium tuberculosis dissemination.
abstract: Protein-subunit vaccines as boosting strategies against tuberculosis (TB) infection are currently in the pipeline of TB vaccine research. Their main limitation is represented by their poor immunogenicity, which makes it necessary to couple protein-subunits with adjuvant molecules. In this study, we employed replication-deficient invasive Escherichia coli strains to deliver Mycobacterium tuberculosis proteins to the cytoplasm of non-phagocytic eukaryotic cells using various priming and prime-boosting vaccination protocols. Our results demonstrate that intranasal administration of invasive E. coli expressing the M. tuberculosis protective antigen MPT64 to mice primed with a recombinant BCG strain over-expressing MPT64 on its surface, decrease bacterial burden in mice spleens. Our data suggest that replication-deficient invasive E. coli may represent a suitable platform for BCG/rBCG priming followed by homologous-boosting immunization strategies.
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Hearth, Largo Gemelli 8, 00168 Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Sali
authors.affiliation: Department of Molecular Medicine, University of Padua, Via Gabelli 63, 35121 Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dainese
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Hearth, Largo Gemelli 8, 00168 Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Morandi
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Hearth, Largo Gemelli 8, 00168 Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zumbo
authors.affiliation: Department of Veterinary, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rocca
authors.affiliation: Department of Microbiology, Institute Pasteur, Rue du Docteur Roux 25-28, 75724 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Goussard
authors.affiliation: Department of Molecular Medicine, University of Padua, Via Gabelli 63, 35121 Padua, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.affiliation: Department of Microbiology, Institute Pasteur, Rue du Docteur Roux 25-28, 75724 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Grillot-Courvalin
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Hearth, Largo Gemelli 8, 00168 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Delogu
authors.affiliation: Department of Molecular Medicine, University of Padua, Via Gabelli 63, 35121 Padua, Italy. Electronic address: riccardo.manganelli@unipd.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Manganelli
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D058491:Bacterial Load; D004926:Escherichia coli; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; C510537:MPT64 protein, Mycobacterium tuberculosis; D011994:Recombinant Proteins; D032581:Tuberculosis Vaccines
keywords: Attenuated vaccines: Mycobacterium tuberculosis; Bactofection; Tuberculosis