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

mRNA vaccines for infectious diseases: principles, delivery and clinical translation. ​

Literature Information ​

DOI10.1038/s41573-021-00283-5
PMID34433919
JournalNature reviews. Drug discovery
Impact Factor101.8
JCR QuartileQ1
Publication Year2021
Times Cited582
KeywordsmRNA vaccines, infectious diseases, lipid nanoparticles, clinical applications
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN1474-1776
Pages817-838
Issue20(11)
AuthorsNamit Chaudhary, Drew Weissman, Kathryn A Whitehead

TL;DR ​

This review explores the evolution and significance of mRNA vaccines, which transitioned from skepticism to clinical application, particularly highlighted during the rapid development in response to the COVID-19 pandemic. It emphasizes the need for further optimization in mRNA design and delivery methods while discussing the potential for mRNA vaccines against a broader range of infectious diseases beyond SARS-CoV-2.

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mRNA vaccines · infectious diseases · lipid nanoparticles · clinical applications

Abstract ​

Over the past several decades, messenger RNA (mRNA) vaccines have progressed from a scepticism-inducing idea to clinical reality. In 2020, the COVID-19 pandemic catalysed the most rapid vaccine development in history, with mRNA vaccines at the forefront of those efforts. Although it is now clear that mRNA vaccines can rapidly and safely protect patients from infectious disease, additional research is required to optimize mRNA design, intracellular delivery and applications beyond SARS-CoV-2 prophylaxis. In this Review, we describe the technologies that underlie mRNA vaccines, with an emphasis on lipid nanoparticles and other non-viral delivery vehicles. We also overview the pipeline of mRNA vaccines against various infectious disease pathogens and discuss key questions for the future application of this breakthrough vaccine platform.

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Primary Questions Addressed ​

  1. What are the specific challenges in optimizing mRNA design for different infectious diseases beyond COVID-19?
  2. How do lipid nanoparticles compare to other non-viral delivery vehicles in terms of efficacy and safety for mRNA vaccines?
  3. What advancements in mRNA vaccine technology are being explored for diseases that have previously lacked effective vaccination strategies?
  4. In what ways can mRNA vaccines be adapted for use in therapeutic applications, such as cancer treatment or autoimmune diseases?
  5. What are the regulatory hurdles faced by mRNA vaccines in different regions, and how do they impact clinical translation?

Key Findings ​

Research Background and Purpose ​

The review discusses the evolution of messenger RNA (mRNA) vaccines, highlighting their rapid development during the COVID-19 pandemic and the necessity for further research to enhance mRNA design, delivery methods, and applications for various infectious diseases beyond SARS-CoV-2. The goal is to provide a comprehensive overview of mRNA vaccine technology, focusing on its principles, delivery mechanisms, and clinical applications.

Main Methods/Materials/Experimental Design ​

The authors detail the technical aspects of mRNA vaccines, particularly the design and synthesis of mRNA and the innovative delivery systems, especially lipid nanoparticles (LNPs). The process is illustrated in the following flowchart:

Mermaid diagram
  1. Sequence Design: The target antigen is designed based on the pathogen's genome.
  2. In Vitro Transcription: Plasmid DNA is transcribed into mRNA using bacteriophage polymerases.
  3. Purification: The mRNA is purified to remove contaminants.
  4. Nanoprecipitation: Purified mRNA is mixed with lipids to form LNPs.
  5. Filtration: Non-aqueous solvents and unencapsulated mRNA are removed.
  6. mRNA Vaccine: The final mRNA vaccine formulation is prepared for storage and distribution.

Key Results and Findings ​

  • mRNA vaccines can be rapidly produced in large quantities, with notable efficacy demonstrated during the COVID-19 pandemic (e.g., Pfizer-BioNTech and Moderna vaccines).
  • LNPs have emerged as the most effective delivery vehicles for mRNA, improving stability and cellular uptake.
  • The review outlines ongoing clinical trials for mRNA vaccines targeting various infectious diseases, including influenza, Zika, and RSV, showcasing the platform's versatility.

Main Conclusions/Significance/Innovation ​

The review concludes that mRNA vaccines represent a significant advancement in vaccination technology, with the potential to respond swiftly to emerging infectious diseases. The rapid development and deployment of COVID-19 vaccines have validated the mRNA platform, prompting further exploration of its applications in prophylactic and therapeutic contexts. The innovations in mRNA design and delivery methods may revolutionize vaccine development and other therapeutic areas.

Research Limitations and Future Directions ​

  • Limitations: The review acknowledges that while mRNA vaccines have shown promise, challenges remain regarding their stability, the need for cold-chain storage, and potential adverse reactions in specific populations.
  • Future Directions: The authors suggest focusing on developing thermostable mRNA vaccines, enhancing delivery systems for targeted immune responses, and exploring the use of mRNA technology for other therapeutic areas, including cancer immunotherapy and protein replacement therapies. There is also a need for further studies on the long-term efficacy and safety of mRNA vaccines in diverse populations, including pregnant individuals and the elderly.
SectionSummary
Research BackgroundmRNA vaccines evolved rapidly during the COVID-19 pandemic; further research is needed for optimization.
MethodsDetailed the design, synthesis, and delivery of mRNA vaccines using lipid nanoparticles.
Key ResultsDemonstrated efficacy of mRNA vaccines; highlighted the role of LNPs in delivery.
ConclusionsmRNA vaccines are a breakthrough in vaccination technology, with potential for broad applications.
LimitationsStability and storage challenges; adverse reactions in specific populations.
Future DirectionsDevelopment of thermostable vaccines; targeted delivery systems; exploration of mRNA in other therapies.

References ​

  1. Structural and molecular mechanisms for the control of eukaryotic 5'-3' mRNA decay. - Jeffrey S Mugridge;Jeff Coller;John D Gross - Nature structural & molecular biology (2018)
  2. Systemic delivery of factor IX messenger RNA for protein replacement therapy. - Suvasini Ramaswamy;Nina Tonnu;Kiyoshi Tachikawa;Pattraranee Limphong;Jerel B Vega;Priya P Karmali;Pad Chivukula;Inder M Verma - Proceedings of the National Academy of Sciences of the United States of America (2017)
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  4. A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria. - Tiffany Sun;Thomas Holowka;Yan Song;Swen Zierow;Lin Leng;Yibang Chen;Huabao Xiong;Jason Griffith;Mehdi Nouraie;Philip E Thuma;Elias Lolis;Chris J Janse;Victor R Gordeuk;Kevin Augustijn;Richard Bucala - Proceedings of the National Academy of Sciences of the United States of America (2012)
  5. Constrained Nanoparticles Deliver siRNA and sgRNA to T Cells In Vivo without Targeting Ligands. - Melissa P Lokugamage;Cory D Sago;Zubao Gan;Brandon R Krupczak;James E Dahlman - Advanced materials (Deerfield Beach, Fla.) (2019)
  6. Prospects for a safe COVID-19 vaccine. - Barton F Haynes;Lawrence Corey;Prabhavathi Fernandes;Peter B Gilbert;Peter J Hotez;Srinivas Rao;Michael R Santos;Hanneke Schuitemaker;Michael Watson;Ann Arvin - Science translational medicine (2020)
  7. Molecular and cellular signatures of human vaccine adjuvants. - F Mosca;E Tritto;A Muzzi;E Monaci;F Bagnoli;C Iavarone;D O'Hagan;R Rappuoli;E De Gregorio - Proceedings of the National Academy of Sciences of the United States of America (2008)
  8. 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)
  9. Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants. - Meng Yuan;Deli Huang;Chang-Chun D Lee;Nicholas C Wu;Abigail M Jackson;Xueyong Zhu;Hejun Liu;Linghang Peng;Marit J van Gils;Rogier W Sanders;Dennis R Burton;S Momsen Reincke;Harald Prüss;Jakob Kreye;David Nemazee;Andrew B Ward;Ian A Wilson - Science (New York, N.Y.) (2021)
  10. Development of lipidoid-siRNA formulations for systemic delivery to the liver. - Akin Akinc;Michael Goldberg;June Qin;J Robert Dorkin;Christina Gamba-Vitalo;Martin Maier;K Narayanannair Jayaprakash;Muthusamy Jayaraman;Kallanthottathil G Rajeev;Muthiah Manoharan;Victor Koteliansky;Ingo Röhl;Elizaveta S Leshchiner;Robert Langer;Daniel G Anderson - Molecular therapy : the journal of the American Society of Gene Therapy (2009)

Literatures Citing This Work ​

  1. COVID-19 and novel mRNA vaccines in pregnancy: an updated literature review. - E Joubert;A C Kekeh;C N Amin - BJOG : an international journal of obstetrics and gynaecology (2022)
  2. Safety, Immunogenicity, Efficacy and Effectiveness of Inactivated Influenza Vaccines in Healthy Pregnant Women and Children Under 5 Years: An Evidence-Based Clinical Review. - Amit Bansal;Mai-Chi Trieu;Kristin G I Mohn;Rebecca Jane Cox - Frontiers in immunology (2021)
  3. A Perspective on Nanotechnology and COVID-19 Vaccine Research and Production in South Africa. - Admire Dube;Samuel Egieyeh;Mohammed Balogun - Viruses (2021)
  4. Two years into COVID-19 - Lessons in SARS-CoV-2 and a perspective from papers in FEBS Letters. - Urs F Greber - FEBS letters (2021)
  5. mRNA vaccines against COVID-19: a showcase for the importance of microbial biotechnology. - Harald Brüssow - Microbial biotechnology (2022)
  6. Initial Screening of Poly(ethylene glycol) Amino Ligands for Affinity Purification of Plasmid DNA in Aqueous Two-Phase Systems. - Nuno R da Silva;Paula Jorge;José A Martins;José A Teixeira;João C Marcos - Life (Basel, Switzerland) (2021)
  7. Advanced Materials for SARS-CoV-2 Vaccines. - Moustafa T Mabrouk;Wei-Chiao Huang;Luis Martinez-Sobrido;Jonathan F Lovell - Advanced materials (Deerfield Beach, Fla.) (2022)
  8. Nucleosides, Nucleotides and Nucleic Acids as Therapeutics: A Virtual Special Issue. - Amanda L Garner - ACS pharmacology & translational science (2021)
  9. Potential implications of lipid nanoparticles in the pathogenesis of myocarditis associated with the use of mRNA vaccines against SARS-CoV-2. - Dimitrios Tsilingiris;Natalia G Vallianou;Irene Karampela;Junli Liu;Maria Dalamaga - Metabolism open (2022)
  10. The Nanoparticle-Enabled Success of COVID-19 mRNA Vaccines and the Promise of Microneedle Platforms for Pandemic Vaccine Response. - Senta M Kapnick - DNA and cell biology (2022)

... (572 more literatures)

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