mRNA vaccine: a potential therapeutic strategy

Abstract

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

Keywords: Antibody-dependent enhancement; COVID-19 mRNA vaccine; Clinical trials; Delivery strategy; Dendritic cell targeting; Immunogenicity; Modification; Non-replicating mRNA; Self-amplifying RNA; mRNA vaccine.

Fig. 1

Antigen-encoding mRNA expression by alphaviral replicon RNA. a DNA plasmid–based saRNA uses plasmid DNA as a carrier to transfer replicase genes and the transgene into the nucleus where the mRNA is translated. b the virus-like particle packages saRNA and delivers replicon RNA to the cytosol by the receptor-mediated endocytosis, forming an endosome. c in vitro transcribed saRNAs are delivered in saline or synthetic formulations. Created with BioRender.com

Fig. 2

Trans-amplifying RNA (taRNA) The replicase transcribes a negative strand RNA with the 3′-nontranslated region (NTR). In turn, it uses the negative strand RNA as a template to transcribe a positive strand RNA from the 5′-NTR region. A promoter (arrow) initiates transcription into mRNA. Vaccine antigens come from the mRNA, which is mediated by cytoplasmic ribosomes. Created with BioRender.com

Fig. 3

Major delivery methods for mRNA vaccines Commonly used delivery methods and carrier molecules for mRNA vaccines are shown: lipid-based delivery, polyer-based delivery, peptide-based delivery, virus-like replicon particle, cationic nanoemulsion, naked mRNAs and dendritic cell-based delivery. Created with BioRender.com