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Are inhaled mRNA vaccines safe and effective? A review of preclinical studies

Evalyne M Jansen1, Henderik W Frijlink1, Wouter Lj Hinrichs1

  • 1Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.

Expert Opinion on Drug Delivery
|October 27, 2022
PubMed
Abstract

Insights

Pulmonary mRNA vaccines offer a potential alternative to injections for boosting immunity against SARS-CoV-2. Preclinical studies suggest this delivery method warrants further investigation for improved vaccine efficacy and administration.

Area of Science:

  • Immunology
  • Vaccinology
  • Pulmonary Drug Delivery

Background:

  • mRNA vaccines, proven effective for SARS-CoV-2, utilize cellular machinery to produce antigens and elicit immune responses.
  • The efficacy of intramuscular mRNA vaccines wanes over time, necessitating frequent booster doses.
  • Pulmonary administration presents a potential strategy to enhance vaccine efficacy and simplify booster regimens.

Approach:

  • This literature study systematically reviewed preclinical (animal) studies on pulmonary mRNA vaccine administration.
  • Searches were conducted in the PubMed/MEDLINE database to identify relevant research.
  • Key areas evaluated included biodistribution, cellular uptake, immune response, protection, and safety.

Key Points:

  • Pulmonary delivery of mRNA vaccines in animal models has been explored for various immunological parameters.
  • Studies assessed how mRNA vaccines distribute within the body, are taken up by cells, and stimulate immune responses after lung delivery.
  • The protective effects and safety profiles of pulmonary mRNA vaccination were also examined in preclinical settings.

Conclusions:

  • Further research is needed to compare the safety and efficacy of pulmonary versus intramuscular mRNA vaccine administration directly.
  • Development of inhalable dry powder formulations for pulmonary mRNA vaccines should be pursued if liquid formulations prove safe and effective.
  • The tolerability of pulmonary mRNA vaccines in patients with pre-existing respiratory conditions requires careful consideration.
Keywords:
Lung deliverySARS-CoV-2mRNA nanoparticlemRNA vaccinemRNA-LNPmucosal immunitypulmonary administration

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