BAXERNA 2.0

ABSTRACT:

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.

AIM (WHAT)

The project BAXERNA 2.0 will establish a new vaccine development pipeline that relies on breakthrough technologies for the development of novel mRNA vaccines against Mycobacterium tuberculosis (MTB), Mycobacterium ulcerans (MU), and Acinetobacter baumannii (AB). The new pipeline will overcome current limitations in vaccine development, namely a lack of known antigens and weak cellular immune responses. The technologies in the new BAXERNA 2.0 pipeline will consist of advances in mass spectrometry-based proteomics and novel vaccines such as mRNA vaccines. The novelty of the project is especially the combined application of these technologies, which will form the blueprint for next-generation bacterial vaccine development.

METHODOLOGY (HOW)

To achieve its ambition, the BAXERNA 2.0 consortium has set up a well-defined plan to carry out the tasks that cluster around the six key objectives of the project: (i) improving proteomics pipeline for identification of substantially more xeno-epitopes; (ii) identifying novel epitopes from MTB, MU, and AB presented by infected cells; (iii) producing novel xeno-epitope mRNA-based lipid nanovaccines; (iv) co-formulating mRNA vaccines with different clinically relevant and broad-spectrum adjuvants; (v) applying prophylactic vaccination in relevant preclinical models; and (vi) carrying out the clinical translation of the top mRNA vaccine for MTB.

IMPACT (WHY)

BAXERNA 2.0 will make significant scientific, technological, economic, and societal contributions. More specifically, the project will increase the knowledge on selected bacterial pathogens and on the role of the immune system in bacterial infections. It will also lead to the development of new technologies for the next generation of antibacterial vaccines. In the long-term, BAXERNA 2.0 will also contribute to decreasing global dependency on antibiotics and will provide a vaccine development pipeline which is ready for rapid response to potential future outbreaks.