Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and sepsis worldwide. Major virulence factors of Nm are the capsular polysaccharides (CPS). Twelve chemically different CPSs have been identified and determine the twelve Nm serogroups, of which six (NmA, -B, -C, -W, -Y and -X) account for virtually all cases of invasive meningococcal disease. Currently, mono- and multivalent glycoconjugate vaccines are available for NmA, -C, -W and -Y and their application has provided most promising results. Though safe and effective, glycoconjugate vaccines are under debate because of high production costs that may limit broad application in afflicted regions. Up until today, the production starts with mass fermentation of pathogens, a step that requires high-tech infrastructure of modern industrial plants and limits the build-up of the production infrastructure in indigent regions like the countries of the African sub-Saharan meningitis belt. However, the need for decentralized vaccine production has become a hot topic as for instance in the 2015 meningitis season, when an NmC outbreak in Niger could not be stopped because of a shortage in vaccine provision. Examples of in vitro synthesized NmA, and NmX CPS, which were proven to be identical to the natural CPSA physicochemical and immunochemical assays, are reported to confirm the technical feasibility at research grade. Also the ability of CRM197 protein conjugates to elicit protective antibodies was confirmed in a mouse model in comparison with conjugates produced by bacterial CPS. The process line outlined for NmA and NmX can be easily tailored for the production of vaccines against other Nm serogroups and thus should have a character model that apply to all glycoconjugate vaccines that start with the biohazardous step of pathogen fermentation.

Exploring the capsule biosynthesis machinery of Neisseria meningitidis: Suitability for in vitro vaccine production

254th National Meeting (2017)

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