Immuno-proteomic analysis of human immune responses to experimental Neisseria meningitidis outer membrane vesicle vaccines identifies potential cross-reactive antigens.
Human volunteers were vaccinated with experimental Neisseria meningitidis serogroup B vaccines based on strain H44/76 detoxified L3 lipooligosaccharide (LOS)-derived outer membrane vesicles (OMV) or the licensed Cuban vaccine, VA-MENGOC-BC. Some volunteers were able to elicit cross-bactericidal antibodies against heterologous L2-LOS strain (760676). An immuno-proteomic approach was used to identify potential targets of these cross-bactericidal antibodies using an L2-LOS derived OMV preparation. A total of nine immuno-reactive spots were detected in this proteome: individuals vaccinated with the detoxified OMVs showed an increase in post-vaccination serum reactivity with Spots 2-8, but not with Spots 1 and 9. Vaccination with VA-MENGOC-BC induced sera that showed increased reactivity with all of the protein spots. Vaccinees showed increases in serum bactericidal activity (SBA) against the heterologous L2-LOS expressing strain 760676, which correlated, in general, with immunoblot reactivity. The identities of proteins within the immuno-reactive spots were determined. These included not only well-studied antigens such as Rmp, Opa, PorB and FbpA (NMB0634), but also identified novel antigens such as exopolyphosphatase (NMB1467) and γ-glutamyltranspeptidase (NMB1057) enzymes and a putative cell binding factor (NMB0345) protein. Investigating the biological properties of such novel antigens may provide candidates for the development of second generation meningococcal vaccines.
Neisseria Research, Molecular Microbiology, Division of Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton Medical School, Southampton SO166YD, United Kingdom.
Jeannette N
JN
Williams
GlaxoSmithKline Vaccines, Rixensart, Belgium.
Vincent
V
Weynants
GlaxoSmithKline Vaccines, Rixensart, Belgium.
Jan T
JT
Poolman
Neisseria Research, Molecular Microbiology, Division of Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton Medical School, Southampton SO166YD, United Kingdom.
John E
JE
Heckels
Neisseria Research, Molecular Microbiology, Division of Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton Medical School, Southampton SO166YD, United Kingdom. Electronic address: mc4@soton.ac.uk.
Myron
M
Christodoulides
D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D017321:Clinical Trials, Phase I as Topic; D003429:Cross Reactions / Q000276:immunology*; D006801:Humans; D022401:Meningococcal Vaccines / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B; D020543:Proteome / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D058248:Serum Bactericidal Antibody Assay
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines; D020543:Proteome
Immuno-proteomics; Neisseria meningitidis; Outer membrane vesicle; Vaccine