Background: Group B , an endotoxin-producing Gram-negative bacterium, causes the highest incidence of group B meningococcus (MenB) disease in the first year of life. The Bexsero vaccine is indicated in Europe from 8 weeks of age. Endotoxin components of outer membrane vesicles (OMVs) or soluble lipopolysaccharide (LPS) represent a potential source of inflammation and residual reactogenicity. The purpose of this study was to compare novel candidate MenB vaccine formulations with licensed vaccines, including Bexsero, using age-specific human culture systems.
Methods: OMVs from wild type- and inactivated gene mutant- strains were characterized in human neonatal and adult whole blood assays and dendritic cell (DC) arrays. OMVs were benchmarked against licensed vaccines, including Bexsero and whole cell pertussis formulations, with respect to Th-polarizing cytokine and prostaglandin E2 production, as well as cell surface activation markers (HLA-DR, CD86, and CCR7). OMV immunogenicity was assessed in mice.
Results: Δ native OMVs (nOMVs) demonstrated significantly less cytokine induction in human blood and DCs than Bexsero and most of the other pediatric vaccines (e.g., PedvaxHib, EasyFive, and bacillus Calmette-Guérin) tested. Despite a much lower inflammatory profile than Bexsero, Δ nOMVs still had moderate DC maturing ability and induced robust anti- antibody responses after murine immunization.
Conclusion: A meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile induces robust antigen-specific immunogenicity .
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| http://dx.doi.org/10.3389/fimmu.2016.00562 | DOI Listing |
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