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mRNA Technology and Mucosal Immunization.

Antonio Toniolo1, Giuseppe Maccari2, Giovanni Camussi3

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This summary is machine-generated.

Plant-derived extracellular vesicles offer a promising approach for mucosal messenger RNA (mRNA) vaccines, enhancing both systemic and mucosal immunity while improving stability and reducing reactogenicity.

Keywords:
combined vaccinationextracellular vesiclesmRNA constructsmRNA vaccinesmucosal immunityplant-derived extracellular vesiclessystemic immunity

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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.