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Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin.

Koeberling, Oliver and 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

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