Lipid Nanoparticles Could Be Effective Carriers for mRNA Vaccines for Viral Lung Infections

Because of their stability and biocompatibility, new research suggests that lipid nanoparticles could be strong candidates for vaccine mRNA transfer against viral lung infections such as influenza, coronavirus, and respiratory syncytial virus (RSV).

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Developing new treatment modalities has become a major goal for researchers of infectious diseases. Nanomedicine is an emerging field that uses nanoscale materials to diagnose or treat diseases, and these materials can also be involved in the targeted delivery of drugs to specific locations around the body.

Similarly, mRNA vaccines are a rapidly developing approach to prevent and control disease. Rather than containing live virus, mRNA vaccines contain a strand of genetic material called mRNA inside a special coating. They provide a strong immune response involving cytotoxic antibodies and T cells, which results in an effective, safe, and long-lasting response. These vaccines are designed to transfer RNA to produce protein antigens to induce the immune response and expression in the target cell.

Nanoparticles could help further optimize the delivery systems of standardized mRNA vaccines. By overcoming biological barriers on both systemic and cellular levels, and by reducing the limitations of free drug molecules, nanoparticles could improve the solubility of drugs, aid in treatment escape from the immune system, and increase the half-life of drugs in the circulatory system. In addition, nanoparticles can deliver drug compounds to work together in the target cell and program to accurately absorb specific drugs, as well as releasing them into the target cell.

In order to achieve targeted delivery, however, nanoparticle drug delivery systems must have certain characteristics. They must first be able to reach specific target tissues, be able to identify them, and delivery the drug, all while preventing or reducing drug-induced damage to healthy tissues. In general, these delivery systems include both nanocapsules and nanospheres.

There are multiple nanoplatforms that can be used to deliver mRNA in the body, although researchers have noted that lipids are the best choice for mRNA transfer due to their fusion compatibility with lipid cell membranes.

The selection of lipid nanoparticles for mRNA vaccine delivery has changed from lipoplexes, cationic nanoemulsions, and traditional liposomes to more advanced solid nanoparticles and nanostructured lipid carriers. Ionizable lipids are considered the most important component of lipid nanoparticles, although other components include cationic lipids, lipid-bound polyethylene glycol (PEG), and cholesterol.

Delivering mRNA based on lipid nanoparticles through endocytosis and then by electrostatic binding is preferable, as well as through fusion with the cell membrane through reverse non-bilayer lipid phases. In delivering mRNA through nanoparticles, lipid nanoparticles have 2 important roles: promotion of the release of mRNA from the endosome to the cytoplasm, and control of the uptake of mRNA into the target host cell.

All of these collective data regarding lipid nanoparticles and their use in mRNA vaccines could have significant impacts in vaccines for influenza, coronavirus, and RSV.

For influenza immunization, the mRNA-1440 and mRNA-1851 vaccines are examples of mRNA vaccines that are composed of lipid nanoparticles. Using a pure nucleoside-modified mRNA encapsulated in lipid nanoparticles that encode various viral surface antigens, Pradi et al. found that these vaccines were cells CD4 and Ts, which induce specific antigens and elicit strong plasma cell responses as well as neutralizing antibodies in mice and non-human mammals. They concluded that combining lipid nanoparticle technology with nucleoside modification was more effective.

Lipid nanoparticle-based mRNA vaccines also show significant potential in coronaviruses, including SARS-CoV, Middle East Respiratory Syndrome, and SARS-CoV-2. Two mRNA-based vaccines—those from Pfizer/BioNTech and Moderna—have been developed using lipid nanoparticles and played crucial roles in diminishing the COVID-19 pandemic and demonstrating the effective use of nanomedicine in combating health problems.

Finally, in RSV, an mRNA vaccine candidate using lipid nanoparticles has been developed for both RSV A and B. It has been shown to express prefusion, although some obstacles still remain in identifying the optimal nanoparticle delivery system.

mRNA vaccines have now demonstrated significant potential as the go-to vaccine technology for viruses that can mutate to escape the immune system. The use of lipid nanoparticles has been key to the development and optimization of the successful mRNA vaccines already on the market, and their beneficial properties have been well established.

Future research should address concerns around biocompatibility, toxicity, and other adverse effects associated with the mRNA and nanoparticle approach. Furthermore, new routes of administration, such as inhalation and nasal or lung targets, may be an opportunity to minimize dosages while maximizing efficacy and raising the most appropriate immune response.

REFERENCE

Asr MH, Dayani F, Segherloo FS, Kamedi A, O’Neill A, MacLoughlin R, et al. Lipid Nanoparticles as Promising Carriers for mRNA Vaccines for Viral Lung Infections. Pharmaceutics. 2023,15(4):1127. doi:10.3390/pharmaceutics15041127