New mRNA - nanoemulsions vaccine platform: application for Tuberculosis vaccine development

Matarazzo, Laura; Taina‑González, Laura; Pinheiro, Ricardo; Pires, David; Fuente, María de la; Bettencourt, Paulo J. G.

http://hdl.handle.net/10400.14/43568

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Authors

Matarazzo, Laura

Taina‑González, Laura

Pinheiro, Ricardo

Pires, David

Fuente, María de la

Bettencourt, Paulo J. G.

Abstract(s)

Background: Tuberculosis (TB) is a deadly infectious disease caused by the airborne bacterium Mycobacterium Tuberculosis (M.tb), killing 1.6 million people every year, especially in low- and middle-income countries. The only licensed TB vaccine, a live attenuated strain of M. bovis (BCG), has variable efficacy, does not prevent transmission and is not safe in immunocompromised patients, particularly AIDS patients, who are at high risk of developing TB disease. Thus, the development of an efficient, safe and cost-effective tuberculosis vaccine remains a research priority. mRNA vaccine technology, which proved its potential during the COVID-19 pandemic, could represent a valuable alternative to conventional vaccines against TB. Objectives: We aim to establish a novel vaccine platform against TB, combining antigen identification by immunopeptidomics, mRNA design and production using advanced techniques, and a patented technology of lipid nanoemulsion (NE) adapted to efficiently deliver mRNA to target cells. Methods: Using a prototype mRNA encoding the fluorescent protein EGFP, we assessed in vitro the safety and transfection efficiency of different NE formulations on human alveolar basal epithelial cells (A549) and primary human monocyte-derived macrophages and dendritic cells. Results: Here we show that NEs can efficiently deliver mRNA to different cell types without significant cytotoxicity, and the formulation can be tailored to increase uptake by specific cells relevant for vaccination applications. Conclusion: Lipid NEs appear to be safe, easily adaptable and efficient transporters for mRNA. We will use selected NE formulations as carriers for mRNA vaccine candidates encoding relevant antigenic peptides from M.tb and other Mycobacterium species. Safety and immunogenicity studies will be performed in mice and the vaccination schedule will be optimized to generate a sustained humoral and cellular immune response against TB. This vaccine platform could be adapted to develop vaccines against other infectious diseases, particularly to quickly respond to emerging pathogens.