mRNA vaccine: a potential therapeutic strategy

被引：285
作者：
Wang, Yang [1 ]
Zhang, Ziqi [1 ]
Luo, Jingwen [1 ]
Han, Xuejiao [1 ]
Wei, Yuquan [1 ]
Wei, Xiawei [1 ]
机构：
[1] Sichuan Univ, Lab Aging Res & Canc Drug Target, State Key Lab Biotherapy, Natl Clin Res Ctr Geriatr,West China Hosp, 17,Block 3,Southern Renmin Rd, Chengdu 610041, Sichuan, Peoples R China
来源：
MOLECULAR CANCER | 2021年 / 20卷 / 01期
关键词：
mRNA vaccine; Self-amplifying RNA; Non-replicating mRNA; Modification; Immunogenicity; Delivery strategy; COVID-19 mRNA vaccine; Clinical trials; Antibody-dependent enhancement; Dendritic cell targeting; ANTIGEN-PRESENTING CELLS; CONSTITUTIVELY ACTIVE TLR4; DENDRITIC CELLS; LIPID NANOPARTICLES; IN-VITRO; T-CELLS; IMMUNE-RESPONSES; STIMULATORY CAPACITY; PROTECTIVE EFFICACY; ANTIBODY-RESPONSES;
D O I：
10.1186/s12943-021-01311-z
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：
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.
引用
收藏
页数：23
相关论文
共 224 条
[1]   COVID-19 and mRNA Vaccines-First Large Test for a New Approach [J].
Abbasi, Jennifer .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 324 (12) :1125-1127
[2]   CD83 expression on dendritic cells and T cells: Correlation with effective immune responses [J].
Aerts-Toegaert, Cindy ;
Heirman, Carlo ;
Tuyaerts, Sandra ;
Corthals, Jurgen ;
Aerts, Joeri L. ;
Bonehill, Aude ;
Thielemans, Kris ;
Breckpot, Karine .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (03) :686-695
[3]   Electroporation as a method of choice to generate genetically modified dendritic cell cancer vaccines [J].
Ahmed, Rita ;
Sayegh, Naya ;
Graciotti, Michele ;
Kandalaft, Lana E. .
CURRENT OPINION IN BIOTECHNOLOGY, 2020, 65 :142-155
[4]   Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial [J].
Alberer, Martin ;
Gnad-Vogt, Ulrike ;
Hong, Henoch Sangjoon ;
Mehr, Keyvan Tadjalli ;
Backert, Linus ;
Finak, Greg ;
Gottardo, Raphael ;
Bica, Mihai Alexandru ;
Garofano, Aurelio ;
Koch, Sven Dominik ;
Fotin-Mleczek, Mariola ;
Hoerr, Ingmar ;
Clemens, Ralf ;
von Sonnenburg, Frank .
LANCET, 2017, 390 (10101) :1511-1520
[5]   A perspective on potential antibody-dependent enhancement of SARS-CoV-2 [J].
Arvin, Ann M. ;
Fink, Katja ;
Schmid, Michael A. ;
Cathcart, Andrea ;
Spreafico, Roberto ;
Havenar-Daughton, Colin ;
Lanzavecchia, Antonio ;
Corti, Davide ;
Virgin, Herbert W. .
NATURE, 2020, 584 (7821) :353-363
[6]   Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses [J].
Bahl, Kapil ;
Senn, Joe J. ;
Yuzhakov, Olga ;
Bulychev, Alex ;
Brito, Luis A. ;
Hassett, Kimberly J. ;
Laska, Michael E. ;
Smith, Mike ;
Almarsson, Orn ;
Thompson, James ;
Ribeiro, Amilcar ;
Watson, Mike ;
Zaks, Tal ;
Ciaramella, Giuseppe .
MOLECULAR THERAPY, 2017, 25 (06) :1316-1327
[7]   Germinal centres and B cell lymphomagenesis [J].
Basso, Katia ;
Dalla-Favera, Riccardo .
NATURE REVIEWS IMMUNOLOGY, 2015, 15 (03) :172-184
[8]   Improved native affinity purification of RNA [J].
Batey, Robert T. ;
Kieft, Jeffrey S. .
RNA, 2007, 13 (08) :1384-1389
[9]   A Trans-amplifying RNA Vaccine Strategy for Induction of Potent Protective Immunity [J].
Beissert, Tim ;
Perkovic, Mario ;
Vogel, Annette ;
Erbar, Stephanie ;
Walzer, Kerstin C. ;
Hempel, Tina ;
Brill, Silke ;
Haefner, Erik ;
Becker, Rene ;
Tureci, Ozlem ;
Sahin, Ugur .
MOLECULAR THERAPY, 2020, 28 (01) :119-128
[10]   mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446 [J].
Bell, Glenn D. ;
Yang, Yi ;
Leung, Euphemia ;
Krissansen, Geoffrey W. .
PLOS ONE, 2018, 13 (07)
12345678910