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mRNA vaccines in disease prevention and treatment.
Literature Information
| DOI | 10.1038/s41392-023-01579-1 |
|---|---|
| PMID | 37726283 |
| Journal | Signal transduction and targeted therapy |
| Impact Factor | 52.7 |
| JCR Quartile | Q1 |
| Publication Year | 2023 |
| Times Cited | 92 |
| Keywords | mRNA vaccines, disease prevention, treatment, technical underpinnings, future prospects |
| Literature Type | Journal Article, Review, Research Support, Non-U.S. Gov't |
| ISSN | 2059-3635 |
| Pages | 365 |
| Issue | 8(1) |
| Authors | Gang Zhang, Tianyu Tang, Yinfeng Chen, Xing Huang, Tingbo Liang |
TL;DR
This review highlights the significant advancements of mRNA vaccines, particularly their efficacy and safety demonstrated during the COVID-19 pandemic, and explores their potential applications across a range of diseases, including cancers and immunological disorders. By examining the technical aspects of mRNA design, synthesis, and delivery, the paper offers insights into current challenges and future directions, making it a valuable resource for researchers and industry professionals.
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mRNA vaccines · disease prevention · treatment · technical underpinnings · future prospects
Abstract
mRNA vaccines have emerged as highly effective strategies in the prophylaxis and treatment of diseases, thanks largely although not totally to their extraordinary performance in recent years against the worldwide plague COVID-19. The huge superiority of mRNA vaccines regarding their efficacy, safety, and large-scale manufacture encourages pharmaceutical industries and biotechnology companies to expand their application to a diverse array of diseases, despite the nonnegligible problems in design, fabrication, and mode of administration. This review delves into the technical underpinnings of mRNA vaccines, covering mRNA design, synthesis, delivery, and adjuvant technologies. Moreover, this review presents a systematic retrospective analysis in a logical and well-organized manner, shedding light on representative mRNA vaccines employed in various diseases. The scope extends across infectious diseases, cancers, immunological diseases, tissue damages, and rare diseases, showcasing the versatility and potential of mRNA vaccines in diverse therapeutic areas. Furthermore, this review engages in a prospective discussion regarding the current challenge and potential direction for the advancement and utilization of mRNA vaccines. Overall, this comprehensive review serves as a valuable resource for researchers, clinicians, and industry professionals, providing a comprehensive understanding of the technical aspects, historical context, and future prospects of mRNA vaccines in the fight against various diseases.
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Primary Questions Addressed
- How do the design and synthesis of mRNA vaccines differ when targeting various types of diseases, such as infectious diseases versus cancers?
- What are the specific challenges associated with the delivery methods of mRNA vaccines, and how might these challenges vary across different therapeutic areas?
- In what ways could advancements in adjuvant technologies enhance the efficacy of mRNA vaccines for treating immunological diseases?
- What lessons learned from the COVID-19 vaccine development can be applied to the future design of mRNA vaccines for rare diseases?
- How might the scalability of mRNA vaccine production impact its application in global health initiatives beyond infectious diseases?
Key Findings
Research Background and Purpose
mRNA vaccines have emerged as a powerful tool for disease prevention and treatment, gaining significant attention due to their success against COVID-19. This review aims to provide a comprehensive overview of the technical aspects, applications, and future prospects of mRNA vaccines across various diseases, including infectious diseases, cancers, immunological disorders, tissue damage, and rare diseases.
Main Methods/Materials/Experimental Design
The development of mRNA vaccines involves several key steps:
mRNA Design: This includes optimizing the sequence for stability and translation efficiency by incorporating elements such as the 5' cap, untranslated regions (UTRs), open reading frames (ORFs), and poly(A) tails.
mRNA Synthesis: In vitro transcription of DNA templates is performed to produce mRNA, followed by purification to ensure the removal of impurities.
Delivery Systems: Various delivery methods, including lipid nanoparticles (LNPs), are utilized to enhance mRNA stability and facilitate cellular uptake.
Adjuvant Technologies: Strategies to enhance the immunogenicity of mRNA vaccines, such as incorporating immune-stimulating components like TriMix, are employed.
Key Results and Findings
- Efficacy and Safety: mRNA vaccines have shown remarkable efficacy and safety profiles, particularly in the context of COVID-19. Clinical trials have demonstrated robust immune responses and minimal adverse effects.
- Versatility: mRNA vaccines have been developed for a wide range of diseases, including:
- Infectious Diseases: Effective against SARS-CoV-2, Zika virus, HIV, and influenza.
- Cancers: Targeting various tumor-associated antigens and neoantigens in melanoma, lung cancer, and more.
- Immunological Diseases: Potential applications in autoimmune conditions and allergies.
- Tissue Damage: Promoting healing in cardiovascular and other tissue injuries.
- Rare Diseases: Addressing genetic disorders such as cystic fibrosis and metabolic diseases.
Main Conclusions/Significance/Innovation
mRNA vaccines represent a transformative approach in medicine, offering rapid development, customization for individual patients, and the potential for widespread application in diverse therapeutic areas. Their ability to elicit strong immune responses makes them a promising modality for combating both infectious diseases and cancers.
Research Limitations and Future Directions
- Storage and Stability: The requirement for ultra-cold storage limits the distribution of mRNA vaccines in resource-limited settings.
- Manufacturing Challenges: Current production methods are time-consuming and complex, necessitating improvements in manufacturing processes.
- Safety Concerns: Although generally safe, the incidence of rare adverse effects (e.g., myocarditis) raises questions about long-term safety.
- Need for Further Research: Continued investigation is necessary to optimize mRNA vaccine formulations, delivery systems, and to explore their efficacy in a broader range of diseases.
Future directions include the exploration of combination therapies, personalized vaccines targeting neoantigens, and improvements in vaccine stability and delivery methods to enhance the overall efficacy and accessibility of mRNA vaccines.
References
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- An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. - Ugur Sahin;Petra Oehm;Evelyna Derhovanessian;Robert A Jabulowsky;Mathias Vormehr;Maike Gold;Daniel Maurus;Doreen Schwarck-Kokarakis;Andreas N Kuhn;Tana Omokoko;Lena M Kranz;Mustafa Diken;Sebastian Kreiter;Heinrich Haas;Sebastian Attig;Richard Rae;Katarina Cuk;Alexandra Kemmer-Brück;Andrea Breitkreuz;Claudia Tolliver;Janina Caspar;Juliane Quinkhardt;Lisa Hebich;Malte Stein;Alexander Hohberger;Isabel Vogler;Inga Liebig;Stephanie Renken;Julian Sikorski;Melanie Leierer;Verena Müller;Heidrun Mitzel-Rink;Matthias Miederer;Christoph Huber;Stephan Grabbe;Jochen Utikal;Andreas Pinter;Roland Kaufmann;Jessica C Hassel;Carmen Loquai;Özlem Türeci - Nature (2020)
- A randomized controlled phase II clinical trial on mRNA electroporated autologous monocyte-derived dendritic cells (TriMixDC-MEL) as adjuvant treatment for stage III/IV melanoma patients who are disease-free following the resection of macrometastases. - Yanina Jansen;Vibeke Kruse;Jurgen Corthals;Kelly Schats;Pieter-Jan van Dam;Teofila Seremet;Carlo Heirman;Lieve Brochez;Mark Kockx;Kris Thielemans;Bart Neyns - Cancer immunology, immunotherapy : CII (2020)
- T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells. - Jon Amund Kyte;Gunnar Kvalheim;Kari Lislerud;Per thor Straten;Svein Dueland;Steinar Aamdal;Gustav Gaudernack - Cancer immunology, immunotherapy : CII (2007)
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- Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. - Shinu John;Olga Yuzhakov;Angela Woods;Jessica Deterling;Kimberly Hassett;Christine A Shaw;Giuseppe Ciaramella - Vaccine (2018)
- Identification of tumor antigens and immune subtypes of cholangiocarcinoma for mRNA vaccine development. - Xing Huang;Tianyu Tang;Gang Zhang;Tingbo Liang - Molecular cancer (2021)
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- A novel, disruptive vaccination technology: self-adjuvanted RNActive(®) vaccines. - Karl-Josef Kallen;Regina Heidenreich;Margit Schnee;Benjamin Petsch;Thomas Schlake;Andreas Thess;Patrick Baumhof;Birgit Scheel;Sven D Koch;Mariola Fotin-Mleczek - Human vaccines & immunotherapeutics (2013)
Literatures Citing This Work
- A novel risk score system based on immune subtypes for identifying optimal mRNA vaccination population in hepatocellular carcinoma. - Hongkai Zhuang;Chenwei Tang;Han Lin;Zedan Zhang;Xinming Chen;Wentao Wang;Qingbin Wang;Wenliang Tan;Lei Yang;Zhiqin Xie;Bingkun Wang;Bo Chen;Changzhen Shang;Yajin Chen - Cellular oncology (Dordrecht, Netherlands) (2024)
- Comparative analysis of antibody responses to BNT162b2, ChAdOx1, and CoronaVac vaccines in the Albanian population over the pandemic years 2021 to 2022. - Genc Sulcebe;Margarita Kurti-Prifti;Erkena Shyti;Jonida Dashi-Pasholli;Fabian Cenko;Alban Ylli - Clinical and experimental vaccine research (2024)
- Recent Findings on Therapeutic Cancer Vaccines: An Updated Review. - Sara Sheikhlary;David Humberto Lopez;Sophia Moghimi;Bo Sun - Biomolecules (2024)
- Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies. - Niloofar Faraji;Tahereh Zeinali;Farahnaz Joukar;Maryam Sadat Aleali;Narges Eslami;Mohammad Shenagari;Fariborz Mansour-Ghanaei - Heliyon (2024)
- The Platform Technology Approach to mRNA Product Development and Regulation. - John H Skerritt;Carolyn Tucek-Szabo;Brett Sutton;Terry Nolan - Vaccines (2024)
- Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice. - Srinivasa Reddy Bonam;Nicholas C Hazell;Mano Joseph Mathew;Yuejin Liang;Xuxiang Zhang;Zhi Wei;Mohamad-Gabriel Alameh;Drew Weissman;Haitao Hu - Vaccines (2024)
- Therapeutic Avenues to Modulate B-Cell Function in Patients With Cardiovascular Disease. - James W O'Brien;Ayden Case;Claudia Kemper;Tian X Zhao;Ziad Mallat - Arteriosclerosis, thrombosis, and vascular biology (2024)
- The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV). - Fatemeh Movahed;Satinik Darzi;Parya Mahdavi;Morug Salih Mahdi;Omer Qutaiba B Allela;Hayder Naji Sameer;Mohaned Adil;Hasna Zarkhah;Saman Yasamineh;Omid Gholizadeh - Virology journal (2024)
- Brief Insights into mRNA Vaccines: Their Successful Production and Nanoformulation for Effective Response against COVID-19 and Their Potential Success for Influenza A and B. - Amerah Parveen;Amal Ali Elkordy - Pathogens (Basel, Switzerland) (2024)
- Potential of mRNA-based vaccines for the control of tick-borne pathogens in one health perspective. - Elizabeth González-Cueto;José de la Fuente;César López-Camacho - Frontiers in immunology (2024)
... (82 more literatures)
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