Vaccines to combat meningococcal disease - definitive vaccines for elusive pathogens
Santos, George F.
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Neisseria meningitidis (Nm) disease occurs worldwide. Disease incidence rates can vary from 1 to 1000 cases per 100,000 with the highest incidence found in the sub-Saharan Africa meningitis belt. Nm has evolved a number of mechanisms to evade host immunity. This includes the production of genetic variants through re-combinatorial events, which is thought to have contributed to the evolution of hyper-invasive lineages that are largely responsible for meningococcal disease. Antigenic diversity of Nm surface proteins has been the main limitation in the design of broadly protective vaccines, particularly against capsular serogroup B strains. To overcome this problem, several Nm genomes have been sequenced in an effort to find highly sequence-conserved surface antigens recognized by the human immune system in order to develop a vaccine, which would be broadly protective against disease. Nm genomes contain over 2 million base pairs that contain between 2000 and 2500 open reading frames. Add to this the difficulty of identifying highly conserved recombinant antigens with strong intrinsic immunostimulatory properties, makes vaccine design and development a daunting task. Recent advances in our understanding of the interactions between innate and acquired immunity, and the discovery of pattern recognition receptors, including Toll-like receptors (TLRs), have ushered in a new set of adjuvant compounds, TLR agonists, which invoke strong humoral and cellular responses with nominal toxicity and adverse reactions. These insights have opened up new areas of vaccine research to combat invasive Nm disease.