Protective biomarkers for the development of novel serotype-independent protein-based vaccine candidates against pneumococcus

Streptococcus pneumoniaethe pneumococcusis the most common cause of severe pneumoniaanddespite the existence of licensed vaccinesannually kills half of a million children under five years old worldwidePneumococcal conjugate vaccinesPCVshave the intrinsic disadvantage of a limited number of serotypes against which they provide protectionresulting in disease due to serotype replacement that reduces their impactA protein based vaccine could be used alone or in combination with PCVs to provide protection against all pneumococcal types in low and middle incomeas well as developed countriesAntigen DiscoveryIncADIof IrvineCalifornia has developed a Spneumoniae pan proteome microarraywith coverage of both the core and accessory geneomewhich can be used to screen antibody responses against the entire pneumococcal proteomeA proteome scale platform for antibody immune profiling has never before been available to the pneumococcus research communityand this technology has the power to rapidly advance our understanding of the protective immune response directed to pneumococcal proteinsThe Respiratory Infections GroupRIGat the Liverpool School of Tropical MedicineLSTMin the U Khas developed a unique human modelwhich allows for the discovery of targets of naturally acquired and vaccine induced immunity against nasal colonization with pneumococciIn the Experimental Human Pneumococcal CarriageEHPCmodelhealthy volunteers are inoculated with a pneumococcal challenge strainand acquisition of the challenge straincarriage positiveor protection from itcarriage negativeas well as immune responses before and after challengeare determined in mucosal secretions and peripheral bloodWe will use pan proteome microarrays to measure the anti protein IgG and IgA levels to specific proteins before bacteria inoculation and associate these responses with protection from carriage using samples from the volunteers of EHPC trialsThis tool will allow us to identify novel relevant protein targets that can be exploited as a part of a multi component or monovalent vaccineWe expect to identify andgtimmunoreactive protein targetsat leastof which are significantly associated with protectionWe will attempt to prioritizeof the most promising candidate antigens to take forward for vaccine development Streptococcus pneumoniaethe pneumococcusis the most common cause of severe pneumoniaanddespite the existence of licensed vaccines against limited number of serotypesannually kills half of a million children under five years old worldwideA new protein microarray developed by Antigen DiscoveryIncwith coverage of the entire pneumoccocal proteome is a technology that provides an opportunity to discover antibodies to target proteins that provide protection against pneumoccoal colonization and invasive diseaseWe will screen antibodies in participants of an Experimental Human Pneumoccocal Carriage trial to identify target proteins of antibodies associated with protection from carriage and take these candidate antigens forward for the development of more effective vaccines against all pneumococcal types