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Identification of immunogenic outer membrane vesicle vaccine antigen components using a meningococcal protein microarray

ABSTRACT: Outer membrane vesicle (OMV)-based vaccines have been employed worldwide in response to epidemic meningococcal disease outbreaks caused by Neisseria meningitidis. The complex composition of OMVs raises challenges in the identification of antigens which contribute to a protective immune response. Here, we measured total IgG antibody binding profiles to a dedicated antigen microarray using human sera from an open-label Phase II trial (NCT00962624) of 4CMenB (Bexsero), a licensed vaccine containing an OMV component. Significant IgG responses were observed against specific Outer Membrane Proteins (OMPs) from OMV antigens, including FetA, PorB, BamA and PorA. Partial Least Squares Regression was used to correlate IgG antibody reactivity profiles with the human complement-dependent killing of meningococci. We show that this approach is a powerful method to identify the potential contributions of OMV antigens - notably OpcA, FetA, PorA and PorB- towards serum bactericidal activity in human vaccinee serum against indicator strains, a recognised correlate of protection against invasive meningococcal disease

ORGANISM(S): Homo sapiens Neisseria meningitidis

PROVIDER: GSE277999 | GEO | 2026/03/02

REPOSITORIES: GEO

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Project description:Vaccines to prevent capsular group B meningococcal disease have been based on proteins, as the polysaccharide capsule was deemed unsuitable due to its similarity to human tissues. Outer membrane vesicle (OMV) vaccines have been targeted at specific capsular group B epidemics in Cuba, Norway, and New Zealand, with the major immunogen determined as porin A (PorA). Subcapsular protein vaccines aim to increase breadth of coverage of meningococcal strains, by the inclusion of protein variants from many different clonal complexes (ccs). Using scalable and portable genomic techniques, it is possible to study the diversity of OMV and subcapsular proteins in relevant meningococcal populations. Shotgun proteomics identified 461 proteins in the OMVs derived from NZ98/254, a component of the Bexsero® vaccine, with a complex proteome comprised of outer membrane proteins and proteins from other cellular compartments. Amino acid sequences for 24 selected proteins were catalogued within the PubMLST Neisseria database as part of the OMV peptide Typing (OMVT) scheme. Of the 24 proteins included, there was variation in the extent of diversity and association with ccs from the most conserved peptides FbpA (NEISp0578) and putative periplasmic proteins (NEISp1063) to the most diverse TbpA (NEISp1690). There were 1752 OMVTs identified amongst 2492/3506 isolates. OMVTs were further grouped into clusters (identical at ≥18 peptide sequences), 45.3% of isolates were assigned to one of 27 OMVT clusters. Both OMVTs and clusters were strongly associated with cc, genogroup and recombinant Bexsero® antigens. The OMVT scheme represents an open-access, web-based tool for the systematic analysis of the multiple components of OMV vaccines, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with both genogroup and Bexsero® Antigen Sequence type (BAST). This highly structured population of disease-causing meningococci is consistent with proposed effects of host immune selection and competition between allelic variants on meningococcal population structure. This has implications for future vaccine assessment, and development, especially the choice of antigen combinations. The methodology is portable and will facilitate region-specific WGS interrogation, allowing informed choices about vaccine development or implementation.

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Identification of immunogenic outer membrane vesicle vaccine antigen components using a meningococcal protein microarray

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