mRNA vaccines for COVID-19: what, why and how

被引:216
作者
Park, Jung Woo [1 ,2 ]
Lagniton, Philip N. P. [1 ,2 ]
Liu, Yu [1 ,2 ]
Xu, Ren-He [1 ,2 ]
机构
[1] Univ Macau, Inst Translat Med, Taipa, Macau, Peoples R China
[2] Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa, Macau, Peoples R China
关键词
COVID-19; SARS-CoV-2; mRNA vaccine; efficacy and safety; CELLULAR IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; SYSTEMIC DELIVERY; IN-VIVO; CODON OPTIMALITY; POLY(A) TAIL; MEMORY B; TRANSLATION; CAP; INDUCTION;
D O I
10.7150/ijbs.59233
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has impacted human lives in the most profound ways with millions of infections and deaths. Scientists and pharmaceutical companies have been in race to produce vaccines against SARS-CoV-2. Vaccine generation usually demands years of developing and testing for efficacy and safety. However, it only took less than one year to generate two mRNA vaccines from their development to deployment. The rapid production time, cost-effectiveness, versatility in vaccine design, and clinically proven ability to induce cellular and humoral immune response have crowned mRNA vaccines with spotlights as most promising vaccine candidates in the fight against the pandemic. In this review, we discuss the general principles of mRNA vaccine design and working mechanisms of the vaccines, and provide an up-to-date summary of pre-clinical and clinical trials on seven anti-COVID-19 mRNA candidate vaccines, with the focus on the two mRNA vaccines already licensed for vaccination. In addition, we highlight the key strategies in designing mRNA vaccines to maximize the expression of immunogens and avoid intrinsic innate immune response. We also provide some perspective for future vaccine development against COVID-19 and other pathogens.
引用
收藏
页码:1446 / 1460
页数:15
相关论文
共 123 条
[91]   Antiviral innate immunity pathways [J].
Seth, RB ;
Sun, LJ ;
Chen, ZJJ .
CELL RESEARCH, 2006, 16 (02) :141-147
[92]   THE CODON ADAPTATION INDEX - A MEASURE OF DIRECTIONAL SYNONYMOUS CODON USAGE BIAS, AND ITS POTENTIAL APPLICATIONS [J].
SHARP, PM ;
LI, WH .
NUCLEIC ACIDS RESEARCH, 1987, 15 (03) :1281-1295
[93]   COVID-19 vaccine development and a potential nanomaterial path forward [J].
Shin, Matthew D. ;
Shukla, Sourabh ;
Chung, Young Hun ;
Beiss, Veronique ;
Chan, Soo Khim ;
Ortega-Rivera, Oscar A. ;
Wirth, David M. ;
Chen, Angela ;
Sack, Markus ;
Pokorski, Jonathan K. ;
Steinmetz, Nicole F. .
NATURE NANOTECHNOLOGY, 2020, 15 (08) :646-655
[94]   Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization [J].
Sioud, M .
JOURNAL OF MOLECULAR BIOLOGY, 2005, 348 (05) :1079-1090
[95]   Protamine sulfate enhances lipid-mediated gene transfer [J].
Sorgi, FL ;
Bhattacharya, S ;
Huang, L .
GENE THERAPY, 1997, 4 (09) :961-968
[96]   Optimization of Synthetic mRNA for Highly Efficient Translation and its Application in the Generation of Endothelial and Hematopoietic Cells from Human and Primate Pluripotent Stem Cells [J].
Suknuntha, Kran ;
Tao, Lihong ;
Brok-Volchanskaya, Vera ;
D'Souza, Saritha S. ;
Kumar, Akhilesh ;
Slukvin, Igor .
STEM CELL REVIEWS AND REPORTS, 2018, 14 (04) :525-534
[97]  
Tanguay RL, 1996, MOL CELL BIOL, V16, P146
[98]   Extracellular RNA Sensing by Pattern Recognition Receptors [J].
Tatematsu, Megumi ;
Funami, Kenji ;
Seya, Tsukasa ;
Matsumoto, Misako .
JOURNAL OF INNATE IMMUNITY, 2018, 10 (5-6) :398-406
[99]   Mechanism of activation of the double-stranded-RNA-dependent protein kinase PKR - Role of dimerization and cellular localization in the stimulation of PKR phosphorylation of eukaryotic initiation factor-2 (elF2) [J].
Vattem, KM ;
Staschke, KA ;
Wek, RC .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (13) :3674-3684
[100]  
Vogel A.B., bioRxiv, V27, DOI DOI 10.1101/2020.12.11.421008