Abstract

There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Lipid nanoparticles (LNPs) have been extensively studied as non-viral vectors for the delivery of mRNA to target cells because of their relatively easy and scalable manufacturing processes. This review highlights key advances in the development of LNPs and reviews the application of mRNA-based vaccines formulated in LNPs for use against infectious diseases and cancer.

Highlights

  • LiposomesLiposomes are spherical vesicles comprising unilamellar or multilamellar phospholipid bilayers enclosing an aqueous core in which the drug of choice can be encapsulated

  • Introduction for RNABased Vaccines.Vaccination is considered an effective approach in controlling infectious diseases.Conventional vaccines based on live attenuated pathogens are known to activate both humoral and cellular immunity

  • The prepared cationic nanoemulsions (CNEs) was used to bind self-amplifying mRNA vaccine encoding the antigens of respiratory syncytial virus (RSV), human immunodeficiency virus (HIV), and human cytomegalovirus

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Summary

Liposomes

Liposomes are spherical vesicles comprising unilamellar or multilamellar phospholipid bilayers enclosing an aqueous core in which the drug of choice can be encapsulated They are prepared from materials possessing polar head (hydrophilic) groups and nonpolar tail (hydrophobic) groups (Figure 2). A potent immune response was observed after subcutaneous injection of mice with mRNA complexed with the cationic lipid 1,2dioleoyl-3-trimethylammonium propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOTAP/DOPE) that encoded the human immunodeficiency virus (HIV)-1 Gag antigen. A range of cationic liposomes, especially those based on 1,2-dioleoyl-3trimethylammonium propane (DOTAP), was proposed to act as vaccine adjuvants These types of cationic liposomes perform as immunomodulators that stimulate the innate immune response in an antigen (or pathogen)-independent manner [58,59]. The potential immune toxicity of cationic liposomes that are employed as delivery systems for nucleic acids must be carefully evaluated

Lipoplexes
Cationic Nanoemulsions
Nanostructured Lipid Carriers
Composition of LNPs
Ionizable Cationic Lipids
Helper Lipids
PEG–Lipids
Cholesterol
Phosphatidylcholines
Methods of Production of LNPs for RNA-Based Vaccines
Route of Administration
Colloidal Stability of Formulations
Incorporation of Targeting Moieties
Incorporation of Adjuvants
Pre-Clinical and Clinical Applications of LNPs as Delivery Systems for
Findings
Conclusions
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