Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin.
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.
Koeberling
Oliver
O
Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, USA. dgranoff@chori.org
Seubert
Anja
A
Granoff
Dan M
DM
D000907:Antibodies, Bacterial / Q000276:immunology*; D000917:Antibody Formation; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics; D001428:Bacterial Vaccines / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D017931:DNA Primers; D004731:Endotoxins; D005784:Gene Amplification; D022401:Meningococcal Vaccines / Q000276:immunology*; D009345:Neisseria meningitidis / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011951:Receptors, Complement / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D017931:DNA Primers; D004731:Endotoxins; D022401:Meningococcal Vaccines; D011951:Receptors, Complement; C484699:factor H-binding protein, Neisseria meningitidis