Abstract
Outer membrane vesicle (OMV)- based vaccines have been used to provide strain-specific protection against capsular group B Neisseria meningitidis infections, but the full breadth of the immune response against the components of the OMV has not been established. Sera from adults vaccinated with an OMV vaccine were used to screen 91 outer membrane proteins (OMPs) incorporated in an antigen microarray panel. Antigen-specific IgG levels were quantified pre-vaccination, and after 12 and 18 weeks. These results were compared with IgG levels from mice vaccinated with the same OMV vaccine. The repertoires of highly responding antigens in humans and mice overlapped, but were not identical. The highest responding antigens to human IgG comprised four integral OMPs (PorA, PorB, OpcA and PilQ), a protein which promotes the stability of PorA and PorB (RmpM) and two lipoproteins (BamC and GNA1162). These observations will assist in evaluating the role of minor antigen components within OMVs in providing protection against meningococcal infection. In addition, the relative dominance of responses to integral OMPs in humans emphasizes the importance of this subclass and points to the value of maintaining conformational epitopes from integral membrane proteins in vaccine formulations.
Highlights
Outer membrane vesicle (OMV)- based vaccines have been used to provide strain-specific protection against capsular group B Neisseria meningitidis infections, but the full breadth of the immune response against the components of the Outer membrane vesicles (OMVs) has not been established
Proteomic analyses of OMVs have identified well over 100 different protein components, including a large number of integral outer membrane proteins which, for the purposes of this paper, we define as proteins where the polypeptide chain completely spans the outer membrane at least once9,10. iOMPs generally form membrane-spanning β-barrel folds and several crystal structures are known for meningococcal proteins[11,12,13,14]
OMVs represent a complex mixture of different antigens, several of which could assist in providing protection
Summary
Outer membrane vesicle (OMV)- based vaccines have been used to provide strain-specific protection against capsular group B Neisseria meningitidis infections, but the full breadth of the immune response against the components of the OMV has not been established. PilQ), a protein which promotes the stability of PorA and PorB (RmpM) and two lipoproteins (BamC and GNA1162) These observations will assist in evaluating the role of minor antigen components within. Capsular group B N. meningitidis (NmB) organisms contribute to most disease cases recorded in developed countries[2], there are safety concerns about the use of capsular group B CPS, as it shares similarities to polysialic acid-containing structures in human foetal brain tissue[3,4]. Outer membrane vesicles (OMVs), which are derived from meningococcal growth cultures by detergent extraction, have been used successfully as vaccines to control clonal outbreaks of NmB infection[5,6,7]. Proteomic analyses of OMVs have identified well over 100 different protein components, including a large number of integral outer membrane proteins (iOMPs) which, for the purposes of this paper, we define as proteins where the polypeptide chain completely spans the outer membrane at least once9,10. iOMPs generally form membrane-spanning β-barrel folds and several crystal structures are known for meningococcal proteins[11,12,13,14]
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