Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines

Figures

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  Fig. 1. The types of structural optimization in non-replicating mRNA vaccines against viral diseases. The optimization mainly contains 5’Cap (The fan of the Purple border), UTR (The fan of the Yellow border), ORF region (The fan of the Cyan border), Poly(A) tail (The fan of the Grey border), and other optimizations (The fan of the Pink border). The purple-edged sector shows the structural modification of 5’cap, mainly including cap1 (m7GpppXmpYp) and ARCA. Cap1 is widely used to develop mRNA vaccines, such as SARS-COV-2, rabies vaccine, etc. ARCA is relatively less used, and is used in influenza vaccines, etc. The yellow-edged sector shows the structural modifications of the UTR region; the main modifications are Kozak sequence (GCCGCCATG), and β-globin. Kozak sequence is used in HIV vaccines and β-globin is used in influenza vaccines. The cyan-edged sector are structural modifications of the ORF region, mainly for codon optimization, such as GC enrichment, for applications to rabies vaccines. The grey-edged sector is the Poly(A) tail, which mostly keeps the mRNA structure stable when its length is less than 300A, and is used in the SARS-COV-2 vaccine and ZIKA vaccine, and etc. The pink…

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  Fig. 2. Structures of non-replicating mRNA vaccines entering clinical trials against viral diseases. The structures of non-replicating mRNA vaccines contain 5’Cap, 5’UTR, ORF region, 3’UTR, and Poly(A) tail. The main difference between the vaccine structures is the material encoded in the ORF regions. This article presents three kinds of mRNA vaccines: preventive mRNA vaccines, antibody-based mRNA vaccines, and mRNA as an immunomodulator. In preventive mRNA vaccine, vaccines against RNA viruses include human metapneumovirus (hMPV), influenza virus (IAV), rabies virus (RABV), SARS-COV-2, ZIKA virus (ZIKV), human Immunodeficiency Virus (HIV), human cytomegalovirus (HCMV) and human papilloma virus (HPV). mRNA vaccines encoding antibodies only contain CHIKV-IgG against CHIKV. mRNA vaccines encode cytokines as an immunomodulator, such as IL-12, which activates the immune response