mRNA Technology and Mucosal Immunization

Area of Science:

• Immunology
• Vaccinology
• Biotechnology

Background:

• Current messenger RNA (mRNA) vaccines primarily induce systemic immunity via intramuscular injection, with limited mucosal immunity.
• Mucosal immunity is crucial for preventing pathogen entry and reducing transmission, but challenges exist in delivering mRNA to mucosal sites.
• Extracellular vesicles (EVs) are being explored as carriers to protect mRNA and reduce reactogenicity for mucosal vaccine applications.

Purpose of the Study:

• To investigate the potential of plant-derived extracellular vesicles as carriers for mucosal mRNA vaccines.
• To evaluate the immunogenicity, stability, and route-dependent efficacy of mRNA-loaded EVs.
• To explore strategies for optimizing mRNA constructs for enhanced vaccine performance.

Main Methods:

• Utilized extracellular vesicles derived from edible fruits (e.g., oranges) to encapsulate mRNA.
• Administered mRNA-loaded EVs via oral, nasal, and intramuscular routes in animal models.
• Assessed systemic and mucosal immune responses, vaccine stability (lyophilization), and potential for mRNA optimization.

Main Results:

• Orange-derived EVs successfully delivered mRNA, eliciting both systemic and mucosal immune responses across different administration routes.
• Lyophilized mRNA-EV formulations demonstrated significant stability.
• mRNA optimization strategies (e.g., 5'cap, poly-A tail, codon selection, nucleoside analogues) can enhance translation, immunogenicity, and stability.

Conclusions:

• Plant-derived EVs are a viable platform for developing stable and effective mucosal mRNA vaccines.
• Mucosal mRNA vaccination, especially when combined with prior parenteral vaccination, holds significant potential for infectious disease prevention and transmission reduction.
• Further research into mRNA optimization and novel constructs (self-amplifying, circular RNA) could advance mucosal vaccine development.