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Abstract
Neisseria meningitidis (meningococcus) is a major causative organism of meningitis and sepsis and Neisseria gonorrhoeae (gonococcus) is the causative organism of the sexually transmitted disease gonorrhea. Infections caused by meningococci are vaccine-preventable, whereas gonococcal vaccine research and development has languished for decades and the correlates of protection are still largely unknown. In the past two decades, complementary ‘omic’ platforms have been developed to interrogate Neisseria genomes and gene products. Proteomic techniques applied to whole Neisseria bacteria, outer membranes and outer membrane vesicle vaccines have generated protein maps and also allowed the examination of environmental stresses on protein expression. In particular, immuno-proteomics has identified proteins whose expression is correlated with the development of human natural immunity to meningococcal infection and colonization and following vaccination. Neisseria proteomic techniques have produced a catalog of potential vaccine antigens and investigating the functional and biological properties of these proteins could finally provide ‘universal’ Neisseria vaccines.
Financial & competing interests disclosure
The author is a named inventor on meningococcal vaccine patents owned by the University of Southampton. The author has received honoraria from Novartis for consultancy: these honoraria were paid into funds administered by the University of Southampton for research purposes only. The author has received funding from GlaxoSmithKline for vaccine studies. Neisseria research is currently funded by the Medical Research Council, UK (Grant MR/K027131/1) and the Wellcome Trust, UK (Grant 090301/Z/09/Z). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Worldwide, Neisseria meningitidis (meningococcus) is still a major causative organism of meningitis and sepsis and sexually transmitted disease caused by Neisseria gonorrhoeae (gonococcus) is emerging as an untreatable disease.
Infections caused by meningococci are vaccine-preventable, although a potential problem with new vaccines is predicted strain coverage.
Gonococcal vaccine research and development has languished for decades and the correlates of protection are still largely unknown.
Neisseria proteomics complements other antigen discovery platforms such as in silico reverse vaccinology and transcriptomics.
Advanced proteomics methods show that the composition of Neisseria outer membranes is complex, containing a large number of proteins with vaccine potential and belonging to different functional classes.
Immuno-proteomics identifies meningococcal proteins associated with the development of protective immunity in humans.
Adaptation of Neisseria spp. to different environments and stresses regulates protein expression and modifies proteomes.
Proteomics has greatly expanded the repertoire of Neisseria outer membrane, surface-exposed and secreted proteins that can be interrogated as potential vaccine candidate antigens, but hypothetical uncharacterized proteins should not be ignored, given the possibility of surface presentation.
High-throughput screening methods that retain protein conformation are urgently needed for assessing the vaccine potential of Neisseria antigens.
Hence, low-throughput and laborious processes are currently used for evaluating vaccine potential; empirical examination of newly identified proteins requires concerted academic and industrial collaborations.