Current Status of Research on mRNA Vaccines Against Viral Infectious Diseases

doi:10.19586/j.2095-2341.2024.0004

Current Biotechnology ›› 2024, Vol. 14 ›› Issue (4): 566-575.DOI: 10.19586/j.2095-2341.2024.0004

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Current Status of Research on mRNA Vaccines Against Viral Infectious Diseases

Yaping HU(), Zhenghong YU()

Jinling Clinical Medical College，Nanjing University of Chinese Medicine，Nanjing 210002，China

Received:2024-01-09 Accepted:2024-05-20 Online:2024-07-25 Published:2024-08-07
Contact: Zhenghong YU

mRNA疫苗预防病毒性传染病的研究现状

胡亚萍(), 于正洪()

南京中医药大学金陵临床医学院，南京 210002

通讯作者: 于正洪
作者简介:胡亚萍 E-mail: 2868240250@qq.com；
基金资助:
2020年后勤科研计划面上项目(CLB20J023)

Abstract

Abstract:

The mRNA vaccine activates the human immune system to produce protective immune responses against specific pathogens by delivering messenger RNA encoding pathogen proteins. The advantages of mRNA vaccines lie in their rapid development， high specificity， and the ability to provide long-term protection through structural optimization， offering a revolutionary new approach for future vaccine development. Currently， mRNA-based vaccines for the prevention of viral infectious diseases have been applied in diseases such as corona virus disease 2019 （COVID-19）， influenza and rabies. This review summarized the development history， structural characteristics， and mechanism of action of mRNA vaccines， elaborated on their application， clinical efficacy， and limitations in several specific viral diseases， proposed the challenges and opportunities faced by mRNA vaccines in responsing to viral infectious diseases， and looked forward to their application prospects in the prevention and control of future viral infectious diseases， with the aim of providing a reference for the research， development and application of mRNA vaccines.

Key words: mRNA vaccine, viral infection, structural characteristics, clinical application

摘要：

mRNA疫苗通过传递编码病原体蛋白的遗传信息信使RNA，激活人体免疫系统产生针对特定病原体的保护性免疫反应。mRNA疫苗的优势在于其快速研发、高度针对性以及可通过结构优化提供长效保护，为未来疫苗研发提供了革命性的新途径。目前，基于mRNA预防病毒传染病的疫苗已经应用于新型冠状病毒感染（corona virus disease 2019，COVID-19）、流感、狂犬病等。总结了mRNA疫苗的研发历程、结构特性以及作用机理，阐述了其在几种特定病毒性疾病中的应用情况、临床效果以及存在的局限性，提出了mRNA疫苗在应对病毒性传染病时所面临的机遇与挑战，并展望了其在未来病毒性传染病防控中的应用前景，以期为mRNA疫苗的研发和应用提供参考。

关键词: mRNA疫苗, 病毒性传染病, 结构特征, 临床应用

CLC Number:

R392-33

Yaping HU, Zhenghong YU. Current Status of Research on mRNA Vaccines Against Viral Infectious Diseases[J]. Current Biotechnology, 2024, 14(4): 566-575.

胡亚萍, 于正洪. mRNA疫苗预防病毒性传染病的研究现状[J]. 生物技术进展, 2024, 14(4): 566-575.

Figures/Tables 4

References 53

1	MCARTHUR D B. Emerging infectious diseases[J]. Nurs. Clin. N. Am., 2019, 54( 2): 297- 311.
2	MURPHY F A. Historical perspective: what constitutes discovery (of a new virus)?[J]. Adv. Virol. Res., 2016, 95: 197- 220.
3	HUI D S C, CHAN P K S. Severe acute respiratory syndrome and coronavirus[J]. Infect. Dis. Clin. N. Am., 2010, 24( 3): 619- 638.
4	GRAÑA C, GHOSN L, EVRENOGLOU T, et al.. Efficacy and safety of COVID-19 vaccines[J/OL]. Cochrane Db. Syst. Rev., 2022, 12( 12): CD015477[ 2024-06-14]. .
5	ZHANG C, MARUGGI G, SHAN H, et al.. Advances in mRNA vaccines for infectious diseases[J/OL]. Front. Immunol., 2019, 10: 594[ 2024-06-14]. .
6	THESS A, GRUND S, MUI B L, et al.. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals[J]. Mol. Ther., 2015, 23( 9): 1456- 1464.
7	SONG J, WANG Q, WU J, et al.. The influence of fluoride ions on the equilibrium between titanium ions and titanium metal in fused alkali chloride melts[J]. Faraday Discuss., 2016, 190: 421- 432.
8	BRENNER S, JACOB F, MESELSON M. An unstable intermediate carrying information from genes to ribosomes for protein synthesis[J]. Nature, 1961, 190: 576- 581.
9	MALONE R W, FELGNER P L, VERMA I M. Cationic liposome-mediated RNA transfection[J]. Proc. Natl. Acad. Sci. USA, 1989, 86( 16): 6077- 6081.
10	WOLFF J A, MALONE R W, WILLIAMS P . et al .. Direct gene transfer into mouse muscle in vivo[J]. Science, 1990, 247( 4949): 1465- 1468.
11	MARTINON F, KRISHNAN S, LENZEN G, et al.. Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA[J]. Eur. J. Immunol., 1993, 23( 7): 1719- 1722.
12	SCHLAKE T, THESS A, FOTIN-MLECZEK M, et al.. Developing mRNA-vaccine technologies[J]. RNA Biol., 2012, 9( 11): 1319- 1330.
13	YOUN H, KCHUNG J. Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy[J]. Expert Opin. Biol. Ther., 2015, 15( 9): 1337- 1348.
14	XIAO W, WANG D. The electrochemical reduction processes of solid compounds in high temperature molten salts[J]. Chem. Soc. Rev., 2014, 43( 10): 3215- 3228.
15	KUHN A N, DIKEN M, KREITER S, et al.. Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo [J]. Gene Ther., 2010, 17( 8): 961- 971.
16	RAUCH S, ROTH N, SCHWENDT K, et al.. mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents[J/OL]. NPJ Vaccines, 2021, 6( 1): 57[ 2024-06-14]. .
17	VERBEKE R, LENTACKER I, DE SMEDT S C, et al.. The dawn of mRNA vaccines: the COVID-19 case[J]. J. Control. Release, 2021, 333: 511- 520.
18	BLAKNEY A K, IP S, GEALL A J. An update on self-amplifying mRNA vaccine development[J/OL]. Vaccines, 2021, 9( 2): 97[ 2024-06-14]. .
19	GREER C E, ZHOU F, LEGG H S, et al.. A chimeric alphavirus RNA replicon gene-based vaccine for human parainfluenza virus type 3 induces protective immunity against intranasal virus challenge[J]. Vaccine, 2007, 25( 3): 481- 489.
20	MOYO N, VOGEL A B, BUUS S, et al.. Efficient induction of T cells against conserved HIV-1 regions by mosaic vaccines delivered as self-amplifying mRNA[J]. Mol. Ther. Methods Clin. Dev., 2019, 12: 32- 46.
21	VOGEL A B, LAMBERT L, KINNEAR E, et al.. Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses[J]. Mol. Ther., 2018, 26( 2): 446- 455.
22	AJBANI S P, VELHAL S M, KADAM R B, et al.. Immunogenicity of virus-like Semliki Forest virus replicon particles expressing Indian HIV-1C gag, env and polRT genes[J]. Immunol. Lett., 2017, 190: 221- 232.
23	KARIKÓ K, BUCKSTEIN M, NI H, et al.. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA[J]. Immunity, 2005, 23( 2): 165- 175.
24	YIN H, KANASTY R L, ELTOUKHY A A, et al.. Non-viral vectors for gene-based therapy[J]. Nat. Rev. Genet., 2014, 15( 8): 541- 555.
25	KORMANN M S D, HASENPUSCH G, ANEJA M K, et al.. Expression of therapeutic proteins after delivery of chemically modified mRNA in mice[J]. Nat. Biotechnol., 2011, 29( 2): 154- 157.
26	MAYS L E, AMMON-TREIBER S, MOTHES B, et al.. Modified Foxp3 mRNA protects against asthma through an IL-10-dependent mechanism[J]. J. Clin. Invest., 2013, 123( 3): 1216- 1228.
27	CHEN G L, LI X F, DAI X H, et al.. Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial[J]. Lancet Microbe, 2022, 3( 3): 193- 202.
28	PARDI N, HOGAN M J, PORTER F W, et al.. mRNA vaccines-a new era in vaccinology[J]. Nat. Rev. Drug Discov., 2018, 17( 4): 261- 279.
29	SAHIN U, KARIKÓ K, TÜRECI Ö. mRNA-based therapeutics-developing a new class of drugs[J]. Nat. Rev. Drug Discov., 2014, 13: 759- 780.
30	BATISTA NAPOTNIK T, POLAJŽER T, MIKLAVČIČ D. Cell death due to electroporation-a review[J/OL]. Bioelectrochem. Amsterdam Neth., 2021, 141: 107871[ 2024-06-14]. .
31	CU Y, BRODERICK K E, BANERJEE K, et al.. Enhanced delivery and potency of self-amplifying mRNA vaccines by electroporation in situ [J]. Vaccines, 2013, 1( 3): 367- 383.
32	GAY C L, DEBENEDETTE M A, TCHEREPANOVA I Y, et al.. Immunogenicity of AGS-004 dendritic cell therapy in patients treated during acute HIV infection[J]. Aids Res. Hum. Retrov., 2018, 34( 1): 111- 122.
33	BELL G D, YANG Y, LEUNG E, et al.. mRNA transfection by a xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446[J/OL]. PLoS ONE, 2018, 13( 7): e 0201464[ 2024-06-14]. .
34	ALDOSARI B N, ALFAGIH I M, ALMURSHEDI A S. Lipid nanoparticles as delivery systems for RNA-based vaccines[J/OL]. Pharmaceutics, 2021, 13( 2): 206[ 2024-06-14]. .
35	RAUCH S, JASNY E, SCHMIDT K E, et al.. New vaccine technologies to combat outbreak situations[J/OL]. Front. Immunol., 2018, 9: 1963[ 2024-06-14]. .
36	CHUNG J Y, THONE M N, KWON Y J. COVID-19 vaccines: the status and perspectives in delivery points of view[J]. Adv. Drug Deliv. Rev., 2021, 170: 1- 25.
37	KOWALCZYK A, DOENER F, ZANZINGER K, et al.. Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity[J]. Vaccine, 2016, 34( 33): 3882- 3893.
38	DU K, ZHENG K, CHEN Z, et al.. Unusual temperature effect on the stability of nickel anodes in molten carbonates[J]. Electrochim. Acta, 2017, 245: 410- 416.
39	CHU L, MCPHEE R, HUANG W, et al.. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine[J]. Vaccine, 2021, 39( 20): 2791- 2799.
40	LAMB Y N. BNT162b2 mRNA COVID-19 vaccine: first approval[J]. Drugs, 2021, 81( 4): 495- 501.
41	DE ALWIS R, GAN E S, CHEN S, et al.. A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice[J]. Mol. Ther., 2021, 29( 6): 1970- 1983.
42	ZHANG N N, LI X F, DENG Y Q, et al.. A thermostable mRNA vaccine against COVID-19[J]. Cell, 2020, 182( 5): 1271- 1283.
43	ALAMEH M G, WEISSMAN D, PARDI N. Messenger RNA-based vaccines against infectious diseases[J]. Curr. Top. Microbiol. Immunol., 2022, 440: 111- 145.
44	FREYN A W, RAMOS DA SILVA J, ROSADO V C, et al.. A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice[J]. Mol. Ther., 2020, 28( 7): 1569- 1584.
45	MCMAHON M, O'DELL G, TAN J, et al.. Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses[J/OL]. Proc. Natl. Acad. Sci. USA, 2022, 119( 45): e 2206333119[ 2024-06-14]. .
46	AREVALO C P, BOLTON M J, LE SAGE V, et al.. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes[J]. Science, 2022, 378( 6622): 899- 904.
47	PARDI N, CARREÑO J M, O'DELL G, et al.. Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses[J/OL]. Nat. Commun., 2022, 13( 1): 4677[ 2024-06-14]. .
48	BAHL K, SENN J J, YUZHAKOV O, et al.. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses[J/OL]. Mol. Ther., 2022, 30( 8): 2874[ 2024-06-14]. .
49	FELDMAN R A, FUHR R, SMOLENOV I, et al.. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials[J]. Vaccine, 2019, 37( 25): 3326- 3334.
50	ALBERER M, GNAD-VOGT U, HONG H S, et al.. 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]. Lancet, 2017, 390( 10101): 1511- 1520.
51	ARMBRUSTER N, JASNY E, PETSCH B. Advances in RNA vaccines for preventive indications: a case study of A vaccine against rabies[J/OL]. Vaccines, 2019, 7( 4): 132[ 2024-06-14]. .
52	DAGAN N, BARDA N, KEPTEN E, et al.. BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting[J]. N. Engl. J. Med., 2021, 384( 15): 1412- 1423.
53	INGLÉS TORRUELLA J, GIL SOTO R M, SABATÉ AGUILA E, et al.. Reactogenicity study of mRNA vaccines against COVID-19[J]. Arch. Prev. Riesgos Labor., 2023, 26( 2): 106- 126.

疫苗类型	设计	稳定性	安全性	免疫原性	缺点
减毒活疫苗	不灵活	差	差	较强	有毒力恢复的风险
灭活病毒疫苗	不灵活	好	较好	较弱	接种剂次多
病毒载体疫苗	灵活	好	一般	强	基因重组风险高
DNA疫苗	灵活	好	好	较弱	基因重组风险高
mRNA疫苗	灵活	差	好	强	长期安全性未知

疫苗类型	设计	稳定性	安全性	免疫原性	缺点
减毒活疫苗	不灵活	差	差	较强	有毒力恢复的风险
灭活病毒疫苗	不灵活	好	较好	较弱	接种剂次多
病毒载体疫苗	灵活	好	一般	强	基因重组风险高
DNA疫苗	灵活	好	好	较弱	基因重组风险高
mRNA疫苗	灵活	差	好	强	长期安全性未知

疫苗名称	来源	特点	效果	储存与运输	安全性	参考文献
mRNA-1273	Moderna	编码封装在新型LNP中的SARS-CoV-2刺突蛋白	免疫原性反应在首次疫苗接种后持续至少119 d，且受到给药剂量的极大影响，预防SARS-CoV-5感染的效力达94.5%	-20 ℃ 下保存和运输（在2~8 ℃ 稳定30 d）	无明显安全问题	[ 38- 39]
mRNA BNT162b2	辉瑞生物科技（美国纽约）	采用多功能脂质颗粒系统配制而成，可引发针对SARS-CoV-2刺突蛋白的免疫原性	注射第1剂后有52%的效力，第2剂后SARS-CoV-2轻度至重度感染病例的效力为95%，这些疫苗在早期保护方面显示出有希望的结果	-70 ℃ 下保存和运输运输（在2~8 ℃ 稳定5 d）	27%的患者在接种部位会出现如红肿瘙痒、乏力、头痛和发热等常见的不良反应	[ 40]
CVnCoV	Curevac（德国蒂宾根）	未经化学修饰，在LNP中配制成mRNA，并编码全长SARS-CoV-2刺突蛋白	该疫苗除了诱导特异性 T细胞反应外，还引发与感染者恢复期血清中表现相当的免疫应答	-	-	[ 16]
ARCT-021	Arcturus Therapeutics（美国加利福尼亚州圣地亚哥）	利用自转录和复制RNA技术，并在脂质启用和解锁的核酸修饰RNA系统中递送	2 μg疫苗在给药60 d后具有增强中和抗体的能力，可诱导强大的CD8 ⁺T细胞和Th1偏向的T辅助	-	-	[ 41]
ARCoV	军事医学科学院、苏州艾博生物和沃森生物	脂质纳米颗粒封装的mRNA ，编码SARS-CoV-2 的受体结合域	可在小鼠模型中提供完全保护	无需冷冻保存，2~8 ℃ 下保持稳定（至少6 个月）	接种后56 d内出现轻中度的不良反应，其中发烧和头痛是最常见	[ 42]

疫苗名称	来源	特点	效果	储存与运输	安全性	参考文献
mRNA-1273	Moderna	编码封装在新型LNP中的SARS-CoV-2刺突蛋白	免疫原性反应在首次疫苗接种后持续至少119 d，且受到给药剂量的极大影响，预防SARS-CoV-5感染的效力达94.5%	-20 ℃ 下保存和运输（在2~8 ℃ 稳定30 d）	无明显安全问题	[ 38- 39]
mRNA BNT162b2	辉瑞生物科技（美国纽约）	采用多功能脂质颗粒系统配制而成，可引发针对SARS-CoV-2刺突蛋白的免疫原性	注射第1剂后有52%的效力，第2剂后SARS-CoV-2轻度至重度感染病例的效力为95%，这些疫苗在早期保护方面显示出有希望的结果	-70 ℃ 下保存和运输运输（在2~8 ℃ 稳定5 d）	27%的患者在接种部位会出现如红肿瘙痒、乏力、头痛和发热等常见的不良反应	[ 40]
CVnCoV	Curevac（德国蒂宾根）	未经化学修饰，在LNP中配制成mRNA，并编码全长SARS-CoV-2刺突蛋白	该疫苗除了诱导特异性 T细胞反应外，还引发与感染者恢复期血清中表现相当的免疫应答	-	-	[ 16]
ARCT-021	Arcturus Therapeutics（美国加利福尼亚州圣地亚哥）	利用自转录和复制RNA技术，并在脂质启用和解锁的核酸修饰RNA系统中递送	2 μg疫苗在给药60 d后具有增强中和抗体的能力，可诱导强大的CD8 ⁺T细胞和Th1偏向的T辅助	-	-	[ 41]
ARCoV	军事医学科学院、苏州艾博生物和沃森生物	脂质纳米颗粒封装的mRNA ，编码SARS-CoV-2 的受体结合域	可在小鼠模型中提供完全保护	无需冷冻保存，2~8 ℃ 下保持稳定（至少6 个月）	接种后56 d内出现轻中度的不良反应，其中发烧和头痛是最常见	[ 42]

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Current Status of Research on mRNA Vaccines Against Viral Infectious Diseases

mRNA疫苗预防病毒性传染病的研究现状

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