Development and Delivery Systems of mRNA Vaccines

Abstract

Since the outbreak of SARS-CoV-2, mRNA vaccine development has undergone a tremendous drive within the pharmaceutical field. In recent years, great progress has been made into mRNA vaccine development, especially in individualized tumor vaccines. mRNA vaccines are a promising approach as the production process is simple, safety profiles are better than those of DNA vaccines, and mRNA-encoded antigens are readily expressed in cells. However, mRNA vaccines also possess some inherent limitations. While side effects such as allergy, renal failure, heart failure, and infarction remain a risk, the vaccine mRNA may also be degraded quickly after administration or cause cytokine storms. This is a substantial challenge for mRNA delivery. However, appropriate carriers can avoid degradation and enhance immune responses, effector presentation, biocompatibility and biosafety. To understand the development and research status of mRNA vaccines, this review focuses on analysis of molecular design, delivery systems and clinical trials of mRNA vaccines, thus highlighting the route for wider development and further clinical trials of mRNA vaccines.

Development of DNA Vaccine Candidate against SARS-CoV-2

“…This is also consolidated by the fact that there is a number of clinical trials of prophylactic DNA vaccines for the prevention of various infectious diseases (NCT04591184, NCT01487876, NCT04445389, NCT01498718, etc.). The technique of developing an mRNA-based vaccine from the beginning to the step of commercialization comprises antigen selection, optimization (addition of immunogenic sequences), plasmid design and synthesis, plasmid transformation into competent bacterial cells, its amplification, extraction, purification, linearization, in vitro transcription of mRNA, purification, capping, packing of mRNA in an effective delivery system, in vitro validation of the antigen expression, in vivo analysis, and ultimately, clinical studies [ 39 , 40 ]. Notably, the DNA vaccine approach also consists of a similar procedure except for the in vitro transcription and other mRNA-related steps meaning that the manufacturing is simpler and time-saving [ 15 ].…”

Developments in Vaccination for Herpes Simplex Virus

“…The classical problems involving the creation of mRNA vaccines include mRNA stability and delivery systems. It remains to be seen whether mRNA vaccines might have a utility for HSV; however, initial studies with the trivalent vaccine have been promising, showing increased efficacy compared to a subunit formulation ( Liu et al, 2021 ).…”

Polymeric Nanoparticles for Inhaled Vaccines

“…The mRNA is encapsulated in the aqueous core of the liposomes to protect it from RNase [ 100 ]. Mostly, lipids are screened by pH-responsive materials because the cationic lipids are easily captured by immune cells [ 101 ]. Norbert et al reported that mRNA encapsulated in lipid nanoparticles can induce high levels of TFH cells and GCB, generate effective neutralizing antibody response and antigen-specific CD4+ T cell response [ 102 ].…”

“…Norbert et al reported that mRNA encapsulated in lipid nanoparticles can induce high levels of TFH cells and GCB, generate effective neutralizing antibody response and antigen-specific CD4+ T cell response [ 102 ]. Polylysine was the first cationic polymer used successfully to deliver plasmid DNA in 1987 [ 101 ]. Since then, other polymers have been used for that purpose such as spermine, chitosan, polyethyleneimine, polyurethane, poly-amido-amine (PAA), polyethylenimine (PEI) and poly-beta amino-esters (PBAEs).…”