Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin.
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Koeberling, Oliver, Seubert, Anja and Granoff, Dan M (2008) Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin. The Journal of Infectious Diseases, 198 (2). pp. 262-270. ISSN 0022-1899
Abstract
BACKGROUND: Outer membrane vesicle (OMV) vaccines from mutant Neisseria meningitidis strains engineered to overexpress factor H-binding protein (fHbp) have elicited broadly protective serum antibody responses in mice. The vaccines investigated were not treated with detergents to avoid extracting fHbp, which is a lipoprotein. Because of their high endotoxin content, the vaccines would not be safe to administer to humans. METHODS: We prepared a native OMV vaccine from a strain engineered to overexpress fHbp and in which the gene encoding LpxL1 was inactivated, which reportedly decreases endotoxin activity. RESULTS: The OMV vaccine from the mutant had a similar or lower ability to induce the expression of proinflammatory cytokines by human peripheral blood mononuclear cells, compared with a detergent-extracted wild-type OMV, and 1000-10,000-fold lower activity than a native wild-type OMV. In mice, the OMV vaccine from the mutant elicited higher serum bactericidal antibody responses to a panel of heterologous N. meningitidis strains than did a control multicomponent recombinant protein vaccine or a detergent-extracted OMV vaccine that has been demonstrated to confer protection against meningococcal disease in humans. CONCLUSIONS: The data illustrate the potential to develop a broadly immunogenic native OMV vaccine that has decreased endotoxin activity and is potentially suitable for testing in humans.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); Embargo of 12 months to 3 years for use in institutional repository; Authors are encouraged to use publisher version (PDF) or link to publisher version |
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| Date Deposited: | 14 Dec 2009 13:53 |
| Last Modified: | 14 Dec 2009 13:53 |
| URI: | https://oak.novartis.com/id/eprint/806 |