OMVs - Vaccine against Pasteurellaceae 100 nm Stefan Schild Institute of Molecular Biosciences University of Graz
market potential human pathogens veterinary pathogens the vaccination market is growing :18 bn US$ in 2009, 28 bn US$ in 2018 mentality is changing towards prevention versus treatment several vaccine opportunities (human and veterinarian) for Pasteurellaceae most relevant indications: species disease vaccine burden non-typeable Haemophilus influenzae (NTHi) HACEK group otitis media, exacerbations in COPD patients, upper respiratory tract infections infective endocarditits, exacerbations in COPD patients, upper respiratory tract infections,... NONE NONE COPD: 3 million deaths in 2004, 3rd leading cause of death by 2030 (source: WHO) Haemophilus ducreyi chancroid NONE increases risk of HIV infection by 10- fold Pasteurella multocida Mannheimia haemolytica Bovine respiratory disease (BRD), pastereullosis Bovine respiratory disease (BRD), respiratory disease in cattle and sheep available, but narrow range protection available, but narrow range protection BRD: 1 bn US$ losses/ year (source: McVey, 2009 and Miles, 2009 in Anim. Health Res.) strains of species within the Pasteurellaceae are too heterogenous for a broad range vaccine
Outer membrane vesicles - OMVs Kuehn and Kesty, 2005 naturally released spherical structures (20-250 nm) non-living facsimiles of the bacteria
OMVs as vaccine candidates Grow bacteria Harvest medium Purify OMVs Resuspend OMVs yield: 3-7 mg/l initial immunization boost boost day 0 day 14 day 28 challenge day 38-39 route: intranasal (oral) dose: 25 µg/immunization (down to 0.25 µg/immunization)
OMVs as vaccine candidates coating antigen strain 1 coating antigen: heterologous strain IM-1 IM-2 IM-2 IM-1 co co challenge with strain 1 challenge with heterologous strain co: PBS treated mice IM-1: mice immunized with OMVs from NTHi strain 1 IM-2: mice immunized with OMVs from NTHi strains 1, 2 and 3
advantages of the OMV-based vaccine highly immunogenic induction of a solid, protective immune response highly immunogenic (protective immune response with <1 µg per animal) simple production simple manufacturing process with high yield (3 to 7 mg/l) easy storaging no need for cold chain stable for one year at RT no need for complex buffer solutions or adjuvants simple administration non-invasive administration (i.e. intranasal or oral) broad protection cross-strain and cross-family protection - mixtures are applicable presentation of a variety bacterial surfaceexposed antigens in their native conformation (most immunogenic antigens identified)
project status research status Roier S, Fenninger CJ, Leitner DR, Rechberger GN, Reidl J, Schild S. 2013. Immunogenicity of Pasteurella multocida and Mannheimia haemolytica outer membrane vesicles. International Journal of Medical Microbiology http://dx.doi.org/10.1016/j.ijmm.2013.05.001 Roier S, Leitner DR, Iwashkiw J, Schild-Prufert K, Feldman MF, Krohne G, Reidl J, Schild S. 2012. Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice. PLoS One 7:e42664 Schild S, Nelson EJ, Camilli A. 2008. Immunization with Vibrio cholerae outer membrane vesicles induces protective immunity in mice. Infect Immun 76:4554-4563 Schild S, Nelson EJ, Bishop AL, Camilli A. 2009. Characterization of Vibrio cholerae outer membrane vesicles as a candidate vaccine for cholera. Infect Immun 77:472-484 Bishop AL, Schild S, Patimalla B, Klein B, Camilli A. 2010. Mucosal immunization with Vibrio cholerae outer membrane vesicles provides maternal protection mediated by antilipopolysaccharide antibodies that inhibit bacterial motility. Infect. Immun. 78:4402-4420 Leitner DR, Feichter S, Schild-Prufert K, Rechberger GN, Reidl J, Schild S. 2013. Lipopolysaccharide-modifications of a cholera vaccine candidate based on outer membrane vesicles reduce the endotoxicity and reveal the major protective antigen. Infect Immun. [Epub ahead of print] 2013 Apr 29. IP status Pending PCT patent application, filed on March 30, 2012 Publication number: WO 2012/131066 Priority date: April 1, 2011
Commercial Oppertunity & Contacts University of Graz offers Technology for licensing and commercialization collaborative future development improve immunization protocol use of OMVs as antigen delivery vehicles test OMVs in a more relevant model (human or animal) Scientific Contact Assoz.-Prof. Dr. Stefan Schild University of Graz Institute of Molecular Biosciences Humbolstrasse 50, 1st floor 8010 Graz Austria tel:++43 316 380 1970 email: stefan.schild@uni-graz.at IP & Business Development Michael Freidl University of Graz Research Management and Service Universitaetsplatz 3 8010 Graz Austria tel:++43 316 380 3994 Email: michael.freidl@uni-graz.at