Nanotechnologies in Delivery of DNA and mRNA Vaccines to the Nasal and Pulmonary Mucosa

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.

Route of self-amplifying mRNA vaccination modulates the establishment of pulmonary resident memory CD8 and CD4 T cells

“…A previous report of self-amplifying RNA delivery by the IN route using multiple delivery systems including LNPs showed poor immunogenicity relative to more typical IM or intradermal injections, and was associated with rapid clearance (56). For the most part, intranasal delivery of mRNA vaccines have been attempted using well-established polymer-based transfection reagents, though such polymer-based approaches have not historically reached clinical application successfully, possibly in part due to toxicity issues (57)(58)(59)(60). Moreover, IN LNP can induce lethal inflammatory responses in mice, complicating studies of alternative administration routes (48).…”

Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge

“…Previous studies from both our group and others have clearly demonstrated that poloxamine-based delivery system mediates significantly better levels of DNA transfection and lower levels of associated inflammatory response in the airways of mouse and pig models than were achieved with the cutting-edge lipid-based formulations 26, 32, 33 . PEI was adopted as a control formulation because it is one of the most well-studied polymer-based gene carrier and has been applied in many mucosal DNA vaccine applications 43 . Although PEI appears to be promising in delivery of mucosal DNA vaccines encoding antigens of Influenza, HIV and SARS-CoV 43 , we found it fails to mediate efficient DNA transfection in the mouse airway, perhaps owing to its poor mucus penetrating properties.…”

“…PEI was adopted as a control formulation because it is one of the most well-studied polymer-based gene carrier and has been applied in many mucosal DNA vaccine applications 43 . Although PEI appears to be promising in delivery of mucosal DNA vaccines encoding antigens of Influenza, HIV and SARS-CoV 43 , we found it fails to mediate efficient DNA transfection in the mouse airway, perhaps owing to its poor mucus penetrating properties. We applied an improved method of preparing nanoparticles without aggregation to enhance the utility of PP-sNp for in vivo applications 44 .…”

Lipid-Based Nano-Sized Cargos as a Promising Strategy in Bone Complications: A Review

“…It is an inexpensive, inert, harmless, fire-resistant, and environmentally friendly approach, in which atomized water droplets are used to coat phospholipid vesicles under high diffusion of carbon dioxide. In this, size and shape can be controlled precisely [ 147 , 148 ]. Cholecalciferol-loaded nanoliposomes were prepared with this approach and 66.7 to 88.9% encapsulation efficiency has been achieved [ 149 ].…”