Bactericidal Antibody Responses Elicited by a Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Factor H–Binding Protein and Genetically Attenuated Endotoxin

• Published in: The Journal of infectious diseases 2008-07, Vol.198 (2), p.262-270
• Main Authors: Koeberling, Oliver, Seubert, Anja, Granoff, Dan M.
• Format: Article
• Language: English
• Subjects: Antibodies; Antibodies, Bacterial - immunology; Antibody Formation; Antigens; Antigens, Bacterial; Applied microbiology; Bacteria; Bacterial Outer Membrane Proteins - immunology; Bacterial Proteins - genetics; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Cytokines; Cytokines - analysis; DNA Primers; Endotoxins; Epidemiology; Fundamental and applied biological sciences. Psychology; Gene Amplification; Infectious diseases; Medical sciences; Meningococcal Vaccines - immunology; Microbiology; Miscellaneous; Monoclonal antibodies; Neisseria meningitidis; Neisseria meningitidis - genetics; Neisseria meningitidis - immunology; Nervous system diseases; Polymerase Chain Reaction; Receptors, Complement - immunology; Recombinant proteins; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/589308

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.