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Injected mRNA vaccines have been proven effective and safe in the SARS-CoV-2 pandemic. Using the machinery of the cell, mRNA vaccines translate into an antigen, which triggers an adaptive immune response. The effectiveness of intramuscular administered mRNA vaccines wanes in the months post-vaccination, which makes frequent booster administrations necessary. To make booster administration easier and increase efficacy, pulmonary administration could be investigated. The aim of this literature study was therefore to review the published preclinical (animal) studies on the safety and efficacy of pulmonary administered mRNA vaccines. We first provide background information on mRNA vaccines and immunological mechanisms of vaccination. Thereafter, we provide an evaluation of published animal studies, in which mRNA vaccines (or mRNA containing nanoparticles) were delivered into the lungs. We covered the following areas: biodistribution, cellular uptake, immune response, protection, and safety. All relevant papers were found using PubMed/MEDLINE database. In our opinion, head-to-head comparison studies examining the safety and efficacy of intramuscular injected and pulmonary administered liquid mRNA vaccines should be performed first. When pulmonary delivered mRNA vaccines are shown to be effective and safe, inhalable dry powder formulations should be engineered. Finally, the tolerability of patients with respiratory diseases should be considered.

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