MenSynVac Study

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.