Next-generation outer membrane vesicle vaccines from concept to clinical trials
Only vaccines containing outer membrane vesicles (OMV) have successfully stopped Neisseria meningitidis serogroup B epidemics. The OMV vaccines, however, provide limited coverage and are difficult to produce. This is caused by an obligatory detergent treatment, which removes lipopolysaccharide (LPS), a toxic OMV component. This thesis explored an alternative approach, based on OMV with attenuated lpxL1-LPS and a detergent-free process. The alternative approach is referred to as ‘next-generation OMV’ and provided vaccines with improved immunological and biochemical properties. In addition, quantitative proteomics demonstrated a preferred protein composition. This provided justification for further development towards clinical trials. After optimization of specific process steps, an improved pilot-scale production process was developed. The quality of OMV from this optimized process was stable and within pre-set specifications for nine consecutive batches. Studies in mice and rabbits suggested that next-generation OMV are immunogenic and safe for parenteral use in humans. Therefore these vaccines are now ready for clinical evaluation. Several groups are developing broadly protective OMV vaccines against N. meningitidis serogroup B, but also against other serogroups and other pathogens. OMV therefore have the potential to become a versatile technology platform for prophylactic and therapeutic vaccines. Such a platform requires a reliable production process to generate substantial quantities of high quality product. The process described in this thesis is well-suited for this purpose. The results encourage technology transfer to a commercial partner, with the goal to translate nextgeneration OMV technology into actual vaccines and improve global public health.
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| Format: | Doctoral thesis biblioteca |
| Language: | English |
| Subjects: | neisseria meningitidis, vaccine development, vaccines, vaccinontwikkeling, vaccins, |
| Online Access: | https://research.wur.nl/en/publications/next-generation-outer-membrane-vesicle-vaccines-from-concept-to-c |
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