Design and evaluation of a LipoParticulate mRNA vaccine carrier, mucus penetrating, able to induce mucosal immune responses against respiratory infectious diseases. – MucRNAvax

The induction of protective immune responses in the respiratory tract remains one of the main challenges in the vaccine field. The emergence and success of messenger RNA (mRNA) vaccines, as seen by the control of Covid-19 pandemic, allowed to envision the induction of specific mucosal immune responses at the portal of entry of respiratory viruses. Indeed, the use of nasal sprays or aerosols carrying mRNA could be an alternative to other routes of vaccination to induce such immune responses. To reach this objective, we propose to develop a new generation of LipoParticles, recently described, composed of a biodegradable core of Poly(Lactic Acid) and of a lipid corona able to protect and pack mRNA, used as aerosols/nasal sprays. The modulation of lipid composition of this corona allows to control the interactions with mucins, favoring particle diffusion through the mucus, thus avoiding their clearance.
Three objectives are identified by the consortium MucRNAvax:
- identify and select muco-penetrating and non-toxic LipoParticles carrying mRNA,
- evaluate their biodistribution (after nasal and pulmonary administration) by whole imaging and correlate their local biodistribution with systemic and mucosal immune responses,
- evaluate the efficacy of this mRNA vaccine vector by comparing three challenge models mastered by consortium members: mRNA of Spike protein (SARS-CoV-2), HA (hemagglutin, Flu) and F (Fusion, RSV).

MucRNAvax gathers four complementary expertise: mRNA vectorology (partner 1), expertise in the culture of pulmonary organoids and respiratory cells (partner 2), knowledge of mucosal and systemic immunity associated with infectious diseases (partner 3), and the mastering of experimental models associated with respiratory viruses, SARS-CoV-2, influenza virus and respiratory virus (RSV) (partner 4). In case of success, this muco-penetrating mRNA delivery system could be extended to other respiratory diseases, of bacterial, genetic or cancer origin.