TY - JOUR
T1 - Are inhaled mRNA vaccines safe and effective? A review of preclinical studies
AU - Jansen, Evalyne M.
AU - Frijlink, Henderik W.
AU - Hinrichs, Wouter L. J.
AU - Ruigrok, Mitchel J. R.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - Introduction: 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. Areas covered: 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. Expert opinion: 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.
AB - Introduction: 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. Areas covered: 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. Expert opinion: 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.
KW - Lung delivery
KW - mRNA nanoparticle
KW - mRNA vaccine
KW - mRNA-LNP
KW - mucosal immunity
KW - pulmonary administration
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85141017474&partnerID=8YFLogxK
U2 - 10.1080/17425247.2022.2131767
DO - 10.1080/17425247.2022.2131767
M3 - Review article
C2 - 36300259
AN - SCOPUS:85141017474
SN - 1742-5247
VL - 19
SP - 1471
EP - 1485
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
IS - 11
ER -