Bacterial meningitis kills 15% of those infected and leaves up to half of survivors with permanent disabilities such as deafness, limb amputations, or learning difficulties, yet current vaccines cannot keep pace with the bacteria's rapidly changing genetics. This research tackles a critical gap: existing vaccines target only some strains of *Neisseria meningitidis* and *Streptococcus pneumoniae*, the two main causes of bacterial meningitis. As these pathogens evolve, vaccine coverage shrinks. The team has already identified conserved surface proteins common across many strains and developed a method to attach a pneumococcal sugar coating to a meningococcal protein using engineered bacteria. The programme now aims to produce a single, low-cost prototype vaccine that protects against both pathogens simultaneously. Researchers will design hybrid antigens using structural biology, attach protective sugars via protein-glycan coupling technology, and then engineer synthetic cells to produce and deliver these glycoconjugate vaccines directly into the human bloodstream. If successful, this would create one of the first synthetic cell vaccines for infectious diseases, potentially transforming how we combat not just meningitis but a wide range of bacterial infections—without the need for expensive, strain-specific reformulations.
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Vaccination is crucial to control of bacterial meningitis because of its devastating 15% mortality rate despite antibiotic intervention, and the development of significant neurological sequelae (deafness, limb amputations, learning disability) in up to 50% of survivors. Currently available vaccines are limited by coverage; the changing genetic epidemiology of the two main aetiological agents of bacterial meningitis, Neisseria meningitidis and Streptococcus pneumoniae, therefore mandates continuous vaccine development efforts. Application of the Reverse Vaccinology 2.0 (RV 2.0) strategy to meningococcal and pneumococcal vaccine antigen discovery in our lab led to the successful identification of highly conserved membrane proteins of novel vaccine candidacy. Other collaborative efforts led to successful glycosylation of a meningococcal surface protein with the pneumococcal serotype 4 glycan using in vivo glycoengineering, thereby providing a platform for cheap production of our novel and exciting vaccine antigens as glycoconjugates. Following from highly promising preliminary work, this research program aims to produce next-generation, low-cost prototype vaccines that will engender further significant decline in the incidence of bacterial meningitis, globally, by: (1) utilising intelligent structural biology tools in the rational design of our exciting targets as hybrid, multi-epitope antigens for enhanced potency of the vaccine-induced immunity; (2) glycosylate these hybrid antigens with the pneumococcal glycan via protein-glycan coupling technology (PGCT), since glycoconjugation offers longer-term protection from disease and asymptomatic infection; and (3) harness the power of synthetic cell (SynCell) engineering for the in vivo production and delivery of these glycoconjugate vaccines into human systemic circulation. The success of this programme would not only result in the successful production of a prototype synthetic cell vaccine (one of the firsts of its kind in the entire field of infectious diseases) to be progressed through follow-on human clinical trial studies, but also a step change in our capability for combating bacterial diseases, in a broader sense.
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