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Curated Papers > Recent high-impact research on "mRNA vaccines" (IF≥30, last 5 years)

mRNA vaccine: a potential therapeutic strategy. ​

Literature Information ​

DOI10.1186/s12943-021-01311-z
PMID33593376
JournalMolecular cancer
Impact Factor33.9
JCR QuartileQ1
Publication Year2021
Times Cited190
KeywordsAntibody-dependent enhancement, COVID-19 mRNA vaccine, Clinical trials, Delivery strategy, Dendritic cell targeting
Literature TypeJournal Article, Research Support, Non-U.S. Gov't, Review
ISSN1476-4598
Pages33
Issue20(1)
AuthorsYang Wang, Ziqi Zhang, Jingwen Luo, Xuejiao Han, Yuquan Wei, Xiawei Wei

TL;DR ​

This paper discusses the advancements in mRNA vaccines, highlighting their potential to combat cancer and viral diseases through enhanced safety and efficacy achieved via sequence optimization and innovative delivery methods. The findings emphasize the importance of understanding mRNA-induced immune responses and the need for further research into the challenges posed by bacterial and parasitic diseases.

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Antibody-dependent enhancement · COVID-19 mRNA vaccine · Clinical trials · Delivery strategy · Dendritic cell targeting

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.

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Primary Questions Addressed ​

  1. How do different delivery strategies impact the efficacy of mRNA vaccines in cancer treatment?
  2. What specific immunological phenomena are observed when using mRNA vaccines against viral diseases compared to traditional vaccines?
  3. In what ways can the optimization of mRNA sequences reduce immunogenicity while maintaining therapeutic effectiveness?
  4. What are the current challenges faced by mRNA vaccines in treating bacterial and parasitic infections, and how might these be addressed?
  5. How do carrier-based mRNA vaccines differ in their mechanisms of action from naked mRNA vaccines in terms of immune response?

Key Findings ​

Research Background and Purpose ​

mRNA vaccines have emerged as a promising therapeutic strategy for combating cancer and viral diseases due to their safety, efficacy, and potential for rapid industrial production. This review aims to explore the advancements in mRNA vaccine technology, focusing on sequence optimization, delivery methods, immunological mechanisms, and their application in clinical trials, particularly in the context of COVID-19 and cancer therapies.

Main Methods/Materials/Experimental Design ​

The review discusses various approaches to enhance mRNA vaccine efficacy, including:

  1. Sequence Optimization: Modifying mRNA sequences to reduce immunogenicity and increase stability.
  2. Delivery Strategies: Exploring different delivery methods such as lipid nanoparticles (LNPs), polymer-based delivery, peptide-based delivery, virus-like replicon particles (VRPs), and naked mRNA vaccines.

Technical Route ​

Mermaid diagram

Key Results and Findings ​

  1. Immunogenicity Reduction: Modifications such as pseudouridine and 5-methylcytidine significantly reduce mRNA immunogenicity while enhancing translation efficiency.
  2. Efficacy of Delivery Systems: LNPs have been shown to protect mRNA from degradation and facilitate cellular uptake, resulting in robust immune responses.
  3. Clinical Trials: Various mRNA vaccines have entered clinical trials, showing promising results against diseases like COVID-19, melanoma, and other cancers.

Main Conclusions/Significance/Innovation ​

The advancements in mRNA vaccine technology represent a significant leap forward in vaccine development, particularly in the rapid response to emerging infectious diseases like COVID-19. The review highlights the versatility of mRNA vaccines in inducing both humoral and cellular immunity, emphasizing their potential not only for viral infections but also for cancer treatment.

Research Limitations and Future Directions ​

While mRNA vaccines demonstrate considerable promise, challenges remain, including:

  • Stability and Immunogenicity: Continued research is necessary to further optimize mRNA stability and minimize unwanted immune responses.
  • Bacterial and Parasitic Diseases: The application of mRNA vaccines to bacterial and parasitic diseases is still in its infancy, warranting further exploration and innovation.
  • Regulatory and Production Hurdles: As mRNA vaccine technologies advance, addressing regulatory challenges and scaling production will be crucial for widespread application.

Future research should focus on refining delivery mechanisms, expanding the scope of diseases targeted by mRNA vaccines, and conducting extensive clinical trials to validate efficacy and safety in diverse populations.

References ​

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  2. Role of 5'- and 3'-untranslated regions of mRNAs in human diseases. - Sangeeta Chatterjee;Jayanta K Pal - Biology of the cell (2009)
  3. A COVID-19 mRNA vaccine encoding SARS-CoV-2 virus-like particles induces a strong antiviral-like immune response in mice. - Jing Lu;Guoliang Lu;Shudan Tan;Jia Xia;Hualong Xiong;Xiaofei Yu;Qingqing Qi;Xiang Yu;Li Li;Hang Yu;Ningshao Xia;Tianying Zhang;Yingjie Xu;Jinzhong Lin - Cell research (2020)
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  6. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. - D Boczkowski;S K Nair;D Snyder;E Gilboa - The Journal of experimental medicine (1996)
  7. mRNA-Lipoplex loaded microbubble contrast agents for ultrasound-assisted transfection of dendritic cells. - Marie-Luce De Temmerman;Heleen Dewitte;Roosmarijn E Vandenbroucke;Bart Lucas;Claude Libert;Jo Demeester;Stefaan C De Smedt;Ine Lentacker;Joanna Rejman - Biomaterials (2011)
  8. Challenges and advances towards the rational design of mRNA vaccines. - Charlotte Pollard;Stefaan De Koker;Xavier Saelens;Guido Vanham;Johan Grooten - Trends in molecular medicine (2013)
  9. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. - Yi Yang;Chia-Wei Li;Li-Chuan Chan;Yongkun Wei;Jung-Mao Hsu;Weiya Xia;Jong-Ho Cha;Junwei Hou;Jennifer L Hsu;Linlin Sun;Mien-Chie Hung - Cell research (2018)
  10. GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha converting enzyme (TACE). - Masahiro Hiasa;Masahiro Abe;Ayako Nakano;Asuka Oda;Hiroe Amou;Shinsuke Kido;Kyoko Takeuchi;Kumiko Kagawa;Kenichiro Yata;Toshihiro Hashimoto;Shuji Ozaki;Kenzo Asaoka;Eiji Tanaka;Keiji Moriyama;Toshio Matsumoto - Blood (2009)

Literatures Citing This Work ​

  1. Vaccination hesitancy and the "myth" on mRNA-based vaccines in Italy in the COVID-19 era: Does urgency meet major safety criteria? - Salvatore Chirumbolo - Journal of medical virology (2021)
  2. Editorial: mRNA Vaccines and Future Epidemic, Pandemic, and Endemic Zoonotic Virus Infections. - Dinah V Parums - Medical science monitor : international medical journal of experimental and clinical research (2021)
  3. Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine. - Dinah V Parums - Medical science monitor : international medical journal of experimental and clinical research (2021)
  4. Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer. - Margaux Saillard;Mara Cenerenti;Pedro Romero;Camilla Jandus - Vaccines (2021)
  5. Engineering of the current nucleoside-modified mRNA-LNP vaccines against SARS-CoV-2. - Javier T Granados-Riveron;Guillermo Aquino-Jarquin - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2021)
  6. Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2. - Marco Palma - Germs (2021)
  7. Vaccine design and delivery approaches for COVID-19. - Kiana Shahzamani;Fatemeh Mahmoudian;Shahrzad Ahangarzadeh;Mohammad Mehdi Ranjbar;Leila Beikmohammadi;Samira Bahrami;Elmira Mohammadi;Sahar Esfandyari;Abbas Alibakhshi;Shaghayegh Haghjooy Javanmard - International immunopharmacology (2021)
  8. Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine. - Hua Zhong;Shuai Liu;Fang Cao;Yi Zhao;Jianguo Zhou;Feng Tang;Zhaohua Peng;Yangsheng Li;Shen Xu;Chunlin Wang;Guohua Yang;Zhi-Qiang Li - Frontiers in immunology (2021)
  9. Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency. - Sun Chang Kim;Simranjeet Singh Sekhon;Woo-Ri Shin;Gna Ahn;Byung-Kwan Cho;Ji-Young Ahn;Yang-Hoon Kim - Molecular & cellular toxicology (2022)
  10. Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2. - Daniela Calina;Antonio F Hernández;Thomas Hartung;Alexey M Egorov;Boris Nikolaevich Izotov;Taxiarchis Konstantinos Nikolouzakis;Aristidis Tsatsakis;Panayiotis G Vlachoyiannopoulos;Anca Oana Docea - Life (Basel, Switzerland) (2021)

... (180 more literatures)

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