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mRNA vaccines - a new era in vaccinology.
Literature Information
| DOI | 10.1038/nrd.2017.243 |
|---|---|
| PMID | 29326426 |
| Journal | Nature reviews. Drug discovery |
| Impact Factor | 101.8 |
| JCR Quartile | Q1 |
| Publication Year | 2018 |
| Times Cited | 2025 |
| Keywords | mRNA vaccines, vaccinology, therapeutic applications |
| Literature Type | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review |
| ISSN | 1474-1776 |
| Pages | 261-279 |
| Issue | 17(4) |
| Authors | Norbert Pardi, Michael J Hogan, Frederick W Porter, Drew Weissman |
TL;DR
mRNA vaccines have emerged as a highly effective alternative to traditional vaccines due to their rapid development and potential for safe, low-cost production, although challenges related to mRNA stability and delivery have limited their use. Recent advancements have addressed these issues, leading to promising results in combating infectious diseases and cancers, highlighting the need for continued research to facilitate their widespread therapeutic application.
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mRNA vaccines · vaccinology · therapeutic applications
Abstract
mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
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Primary Questions Addressed
- What are the specific challenges faced in the delivery of mRNA vaccines, and how have recent technological advancements addressed these issues?
- In what ways do mRNA vaccines compare to traditional vaccines in terms of efficacy and safety for different infectious diseases?
- How can the rapid development of mRNA vaccine platforms be leveraged for future pandemics or emerging infectious diseases?
- What are the potential implications of mRNA vaccines in the treatment of various types of cancer beyond infectious diseases?
- What regulatory and ethical considerations need to be addressed as mRNA vaccines move towards widespread therapeutic use?
Key Findings
Research Background and Purpose
mRNA vaccines have emerged as a groundbreaking alternative to traditional vaccine approaches, offering advantages such as rapid development, high potency, and potential for low-cost manufacturing. Despite their promise, earlier applications were limited due to challenges related to mRNA instability and inefficient delivery. This review explores the advancements in mRNA vaccine technology, its applications against infectious diseases and cancer, and the future challenges and directions in the field.
Main Methods/Materials/Experimental Design
The review outlines the evolution of mRNA vaccine platforms, detailing key advancements that have improved their stability, delivery, and immunogenicity. Key strategies include:
- mRNA Engineering: Modifications to enhance stability and reduce immunogenicity, such as incorporating modified nucleosides (e.g., pseudouridine) and optimizing codon usage.
- Delivery Systems: Various carriers (lipid nanoparticles, cationic polymers, and protamine) have been developed to protect mRNA from degradation and facilitate cellular uptake.
Key Results and Findings
- Safety and Efficacy: mRNA vaccines have demonstrated favorable safety profiles in animal models and initial human trials, showing the ability to induce robust immune responses against various pathogens.
- Applications in Infectious Diseases: mRNA vaccines have shown promise against diseases like influenza, Zika, and HIV, with both self-amplifying and non-replicating mRNA formats being utilized.
- Cancer Vaccines: Personalized neoepitope vaccines have been developed using mRNA, targeting unique tumor mutations, with encouraging results in clinical trials.
Main Conclusions/Significance/Innovation
The review concludes that mRNA vaccines represent a transformative approach in vaccinology, capable of addressing challenges in both infectious disease and cancer immunotherapy. Their rapid development and adaptability to emerging pathogens highlight their potential as a cornerstone of future vaccine strategies. Innovations in mRNA engineering and delivery methods are pivotal for enhancing the efficacy and safety of these vaccines.
Research Limitations and Future Directions
While preclinical data is promising, recent clinical trials have shown that human responses may not always match animal model results, necessitating further investigation. Future research should focus on:
- Understanding the mechanisms of innate immune sensing of mRNA.
- Developing more efficient delivery systems that target specific cell types.
- Exploring combination therapies that integrate mRNA vaccines with traditional treatments to enhance therapeutic outcomes.
| Aspect | Current Status | Future Direction |
|---|---|---|
| Efficacy in Humans | Modest responses compared to animal models | Further studies to enhance immunogenicity |
| Delivery Mechanisms | Various systems in development (e.g., LNPs, polymers) | Targeted delivery to specific immune cells |
| Applications | Effective against several infectious diseases and cancer | Expansion to more diseases and personalized medicine |
This structured summary encapsulates the essence of the review on mRNA vaccines, emphasizing their innovative potential and the critical need for ongoing research to optimize their application in public health.
References
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Literatures Citing This Work
- New Kids on the Block: RNA-Based Influenza Virus Vaccines. - Francesco Berlanda Scorza;Norbert Pardi - Vaccines (2018)
- Tapping the RNA world for therapeutics. - Judy Lieberman - Nature structural & molecular biology (2018)
- Vaccines work. - Nature communications (2018)
- Nanoscale platforms for messenger RNA delivery. - Bin Li;Xinfu Zhang;Yizhou Dong - Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology (2019)
- Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. - Norbert Pardi;Michael J Hogan;Martin S Naradikian;Kaela Parkhouse;Derek W Cain;Letitia Jones;M Anthony Moody;Hans P Verkerke;Arpita Myles;Elinor Willis;Celia C LaBranche;David C Montefiori;Jenna L Lobby;Kevin O Saunders;Hua-Xin Liao;Bette T Korber;Laura L Sutherland;Richard M Scearce;Peter T Hraber;István Tombácz;Hiromi Muramatsu;Houping Ni;Daniel A Balikov;Charles Li;Barbara L Mui;Ying K Tam;Florian Krammer;Katalin Karikó;Patricia Polacino;Laurence C Eisenlohr;Thomas D Madden;Michael J Hope;Mark G Lewis;Kelly K Lee;Shiu-Lok Hu;Scott E Hensley;Michael P Cancro;Barton F Haynes;Drew Weissman - The Journal of experimental medicine (2018)
- Exploiting vita-PAMPs in vaccines. - J Magarian Blander;Gaetan Barbet - Current opinion in pharmacology (2018)
- Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters. - Colin J McKinlay;Nancy L Benner;Ole A Haabeth;Robert M Waymouth;Paul A Wender - Proceedings of the National Academy of Sciences of the United States of America (2018)
- Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis. - Ema Robinson;Kelvin D MacDonald;Kai Slaughter;Madison McKinney;Siddharth Patel;Conroy Sun;Gaurav Sahay - Molecular therapy : the journal of the American Society of Gene Therapy (2018)
- Harnessing T Follicular Helper Cell Responses for HIV Vaccine Development. - Julia Niessl;Daniel E Kaufmann - Viruses (2018)
- Zika virus vaccines. - Peter Abbink;Kathryn E Stephenson;Dan H Barouch - Nature reviews. Microbiology (2018)
... (2015 more literatures)
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