Abstract
Recent advancements in the field of in vitro transcribed mRNA (IVT-mRNA) vaccination have attracted considerable attention to such vaccination as a cutting-edge technique against infectious diseases including COVID-19 caused by SARS-CoV-2. While numerous pathogens infect the host through the respiratory mucosa, conventional parenterally administered vaccines are unable to induce protective immunity at mucosal surfaces. Mucosal immunization enables the induction of both mucosal and systemic immunity, efficiently removing pathogens from the mucosa before an infection occurs. Although respiratory mucosal vaccination is highly appealing, successful nasal or pulmonary delivery of nucleic acid-based vaccines is challenging because of several physical and biological barriers at the airway mucosal site, such as a variety of protective enzymes and mucociliary clearance, which remove exogenously inhaled substances. Hence, advanced nanotechnologies enabling delivery of DNA and IVT-mRNA to the nasal and pulmonary mucosa are urgently needed. Ideal nanocarriers for nucleic acid vaccines should be able to efficiently load and protect genetic payloads, overcome physical and biological barriers at the airway mucosal site, facilitate transfection in targeted epithelial or antigen-presenting cells, and incorporate adjuvants. In this review, we discuss recent developments in nucleic acid delivery systems that target airway mucosa for vaccination purposes.
Highlights
Publisher’s Note: MDPI stays neutralIn recent decades, nanotechnologies for the production of high-quality nucleic acids and efficient in vivo delivery systems have revolutionized the field of vaccine development [1,2,3,4]
Several limitations of this study should be kept in mind: (1) the findings focused on lipid nanoparticles (LNPs) containing 7C1, but more research is needed to quantify the link between LNP composition and nebulized delivery; (2) more studies are needed to quantify the link between payload and delivery efficiency, as the protein expression kinetics observed may vary depending on the IVT-mRNA payload; (3) these findings, from mice models, may or may not translate predictably to larger animals, such as nonhuman primates; (4) LNP size and zeta potential, as well as other altered physiologies associated with diseased pulmonary tissues, may impede pulmonary LNP delivery
To overcome the mechanical–physical barriers of the respiratory tract, developing safe and efficient delivery systems is crucial for the successful clinical translation of NAvaccines, as proven by the LNP delivery system in coronavirus disease (COVID)-19 mRNA vaccines
Summary
Nanotechnologies for the production of high-quality nucleic acids and efficient in vivo delivery systems have revolutionized the field of vaccine development [1,2,3,4]. Nucleic acid-based vaccines (NA-vaccines) utilize affordable and well-established standard manufacturing processes that can scale up rapidly in response to outbreaks of infectious diseases, avoiding the complex procedures of repeated culture and inactivation of infectious pathogens or purification of recombinant antigens [5,14]. These genetic vaccines offer several distinct advantages over conventional vaccines (Table 1). Moderna’s 1273-mRNA vaccine and BioNTech’s 162b2-mRNA vaccine finished phase III clinical trials with 94–95% effectiveness in protection against COVID-19 and obtained emergency use authorization within one year from the outbreak of the virus [26,27]
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