Immunopeptidomics-based Development of Next-Generation Bacterial mRNA Vaccines

BAXERNA 2.0 will establish a new vaccine development pipeline based on dramatically improved immunopeptidomics screening and innovative mRNA vaccine formulation. We will use our powerful new pipeline to develop novel mRNA vaccines against three bacterial pathogens that can persist within phagocytic cells: Mycobacterium tuberculosis (MTB), Mycobacterium ulcerans (MU), and Acinetobacter baumannii (AB). MTB and AB are clinically problematic bacteria with alarming levels of antimicrobial resistance (AMR), while MU is an important neglected tropical disease. Although vaccines are recognized as highly effective tools to mitigate AMR and tropical diseases, effective vaccine development for these (facultative) intracellular bacteria is held back by a lack of known antigens, and by current vaccine platforms struggling to elicit the required strong cellular immune responses. We will overcome both limitations here through two key innovations: (i) novel proteomics and proteomics informatics approaches for immunopeptidomics to allow highly sensitive discovery and prioritization of bacterial epitopes presented on infected cells; and (ii) novel mRNA vaccines to induce both humoral and cellular immune responses, with innovative adjuvants to strengthen adaptive immunity, and to modulate innate immunity. Vaccine production will be done according to GMP standards, and we will pursue novel, low-cost production methods to enable local production and much-needed improved vaccine stability.We will characterize innate and adaptive immune responses in detail in human cellular models and mouse infection models. In addition, top vaccine candidates for MTB will be evaluated in unique primate models, followed by testing of the lead candidate in a first-in-human Phase I clinical trial.Together, we will establish our novel vaccine development pipeline as a blueprint for world-leading, next-generation bacterial vaccine development.