Protective antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed genome-derived neisserial antigen 1870.
Background. Meningococcal outer membrane vesicle (OMV) vaccines are efficacious in humans but have serosubtype-specific serum bactericidal antibody responses directed at the porin protein PorA and the potential for immune selection of PorA-escape mutants.Methods. We prepared an OMV vaccine from a Neisseria meningitidis strain engineered to overexpress genome-derived neisserial antigen (GNA) 1870, a lipoprotein discovered by genome mining that is being investigated for use in a vaccine.Results. Mice immunized with the modified GNA1870-OMV vaccine developed broader serum bactericidal antibody responses than control mice immunized with a recombinant GNA1870 protein vaccine or an OMV vaccine prepared from wild-type N. meningitidis or a combination of vaccines prepared from wild-type N. meningitidis and recombinant protein. Antiserum from mice immunized with the modified GNA1870-OMV vaccine also elicited greater deposition of human C3 complement on the surface of live N. meningitidis bacteria and greater passive protective activity against meningococcal bacteremia in infant rats. A N. meningitidis mutant with decreased expression of PorA was more susceptible to bactericidal activity of anti-GNA1870 antibodies.Conclusions. The modified GNA1870-OMV vaccine elicits broader protection against meningococcal disease than recombinant GNA1870 protein or conventional OMV vaccines and also has less risk of selection of PorA-escape mutants than a conventional OMV vaccine.
Hou
Victor C
VC
Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
Koeberling
Oliver
O
Welsch
Jo Anne
JA
Granoff
Dan M
DM
D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000097:blood*; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000276:immunology*; D016470:Bacteremia / Q000517:prevention & control; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D003176:Complement C3 / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D051381:Rats
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003176:Complement C3; D022401:Meningococcal Vaccines; C488465:antigen 1870, Neisseria meningitidis