A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity.

Autor:	Dowling DJ; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Sanders H; Janssen Vaccines and Prevention B.V. , Leiden , Netherlands., Cheng WK; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Precision Vaccine Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA., Joshi S; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Precision Vaccine Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA., Brightman S; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Precision Vaccine Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA., Bergelson I; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital , Boston, MA , USA., Pietrasanta C; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Precision Vaccine Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy., van Haren SD; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Precision Vaccine Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA., van Amsterdam S; Janssen Vaccines and Prevention B.V. , Leiden , Netherlands., Fernandez J; Janssen Research and Development, LLC , Spring House, PA , USA., van den Dobbelsteen GP; Janssen Vaccines and Prevention B.V. , Leiden , Netherlands., Levy O; Department of Medicine, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Precision Vaccine Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2016 Dec 08; Vol. 7, pp. 562. Date of Electronic Publication: 2016 Dec 08 (Print Publication: 2016).
DOI:	10.3389/fimmu.2016.00562
Abstrakt:	Background: Group B Neisseria meningitidis , 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 in vitro culture systems. Methods: OMVs from wild type- and inactivated lpxL1 gene mutant- N. meningitidis strains were characterized in human neonatal and adult in vitro 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 lpxLI 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 in vitro than Bexsero, Δ lpxLI nOMVs still had moderate DC maturing ability and induced robust anti- N. meningitidis antibody responses after murine immunization. Conclusion: A meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile in vitro induces robust antigen-specific immunogenicity in vivo .
Databáze:	MEDLINE
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