Spontaneously released Neisseria meningitidis outer membrane vesicles as vaccine platform: production and purification |
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Institution: | 1. Institute for Translational Vaccinology (Intravacc), Process Development Bacterial Vaccines, P.O. Box 450, 3720 AL Bilthoven, the Netherlands;2. Wageningen University, Bioprocess Engineering, P.O. Box 16, 6700 AA Wageningen, the Netherlands;3. Nord University, Faculty of Biosciences and Aquaculture, P.O. Box 1409, 8049 Bodø, Norway;4. Institute for Translational Vaccinology (Intravacc), Exploratory & Clinical Research, P.O. Box 450, 3720 AL Bilthoven, the Netherlands;1. Department of Bioengineering, McGill University, Montreal, Canada;2. Protein Expression Facility, The University of Queensland, Brisbane, Australia;3. Merck Research Laboratories, West Point, PA, USA |
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Abstract: | Outer membrane vesicles (OMVs) are nanoparticles produced by Gram-negative bacteria that can be used as vaccines. The application of OMVs as vaccine component can be expanded by expressing heterologous antigens on OMVs, creating an OMV-based antigen presenting platform. This study aims to develop a production process for such OMV-based vaccines and studies a production method based on meningococcal OMVs that express heterologous antigens on their surface. As a proof of concept, the Borrelia burgdorferi antigens OspA and OspC were expressed on Neisseria meningitidis OMVs to create a concept anti-Lyme disease vaccine. Production of OMVs released in the culture supernatant was induced by high dissolved oxygen concentrations and purification was based on scalable unit operations. A crude recovery of 90 mg OMV protein could be obtained per liter culture. Expressing heterologous antigens on the OMVs did result in minor reduction of bacterial growth, while OMV production remained constant. The antigen expression did not alter the OMV characteristics. This study shows that production of well characterized OMVs containing heterologous antigens is possible with high yields by combining high oxygen concentrations with an optimized purification process. It is concluded that heterologous OMVs show potential as a vaccine platform. |
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Keywords: | Outer membrane vesicles Vaccine Vaccine platform Tangential flow filtration Lyme disease |
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