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Curated Papers > High-impact authoritative literature on "mRNA vaccines"

Advances in mRNA Vaccines for Infectious Diseases. ​

Literature Information ​

DOI10.3389/fimmu.2019.00594
PMID30972078
JournalFrontiers in immunology
Impact Factor5.9
JCR QuartileQ1
Publication Year2019
Times Cited353
Keywordsapplication, delivery, infectious disease, mRNA vaccine, mechanism
Literature TypeJournal Article, Research Support, Non-U.S. Gov't, Review
ISSN1664-3224
Pages594
Issue10()
AuthorsCuiling Zhang, Giulietta Maruggi, Hu Shan, Junwei Li

TL;DR ​

This review discusses the significant advancements in RNA-based technologies, particularly mRNA vaccines, which have demonstrated safety and durability in eliciting immune responses in both preclinical and clinical studies. The findings underscore the potential of mRNA vaccines as rapid-response tools for combating infectious diseases, emphasizing their promising future in vaccine design and application.

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application · delivery · infectious disease · mRNA vaccine · mechanism

Abstract ​

During the last two decades, there has been broad interest in RNA-based technologies for the development of prophylactic and therapeutic vaccines. Preclinical and clinical trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans. In this review, we summarize current research progress on mRNA vaccines, which have the potential to be quick-manufactured and to become powerful tools against infectious disease and we highlight the bright future of their design and applications.

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Primary Questions Addressed ​

  1. What specific infectious diseases have shown the most promise for mRNA vaccine development?
  2. How do mRNA vaccines compare to traditional vaccine platforms in terms of manufacturing speed and immune response?
  3. What are the key challenges faced in the clinical trials of mRNA vaccines for infectious diseases?
  4. In what ways can mRNA vaccine technology be adapted for use against emerging infectious diseases?
  5. How might the future of mRNA vaccines impact global vaccination strategies and public health policies?

Key Findings ​

Research Background and Objectives ​

Vaccination has historically been a cornerstone of public health, significantly reducing morbidity and mortality from infectious diseases. Traditional vaccine development has often relied on inactivated or live attenuated pathogens, which come with limitations such as safety concerns and the need for cold-chain logistics. The emergence of RNA-based technologies, particularly mRNA vaccines, has generated renewed interest due to their rapid production capabilities and potential for robust immune responses. This review aims to summarize recent advances in mRNA vaccine technology, emphasizing their applications in infectious disease prevention and treatment.

Main Methods/Materials/Experimental Design ​

The review discusses the mechanisms of mRNA vaccines, focusing on two main types: conventional mRNA vaccines and self-amplifying mRNA vaccines. The manufacturing process involves in vitro transcription of mRNA from a linearized plasmid DNA template, followed by purification and formulation into delivery vehicles such as lipid nanoparticles (LNPs).

The technical route can be illustrated as follows:

Mermaid diagram
  1. In vitro Transcription: mRNA is synthesized using a DNA template and RNA polymerase.
  2. Purification: The synthesized mRNA is purified to remove contaminants that could inhibit translation.
  3. Formulation: mRNA is encapsulated in delivery vehicles, such as LNPs, to enhance stability and delivery efficiency.
  4. Delivery: mRNA is administered via various routes (intramuscular, intradermal, etc.) to induce an immune response.
  5. Immune Response: The delivered mRNA is translated into proteins, eliciting T and B cell responses.

Key Results and Findings ​

  • mRNA vaccines demonstrate significant advantages over traditional vaccines, including rapid production, safety (non-infectious), and the ability to elicit both humoral and cellular immune responses.
  • Self-amplifying mRNA vaccines can produce higher levels of antigen with lower doses compared to conventional mRNA vaccines.
  • Clinical trials show promising safety and immunogenicity profiles for mRNA vaccines targeting various infectious diseases, including influenza and rabies.
  • The use of modified nucleotides in mRNA enhances stability and translation efficiency while reducing immunogenicity.

Main Conclusions/Significance/Innovation ​

The review concludes that mRNA vaccines represent a novel and flexible platform for rapid vaccine development, particularly in response to emerging infectious diseases. Their ability to be produced quickly and efficiently positions them as crucial tools in pandemic preparedness. Furthermore, the advancements in delivery systems and formulation strategies enhance their efficacy and stability, paving the way for broader applications in both infectious disease prevention and cancer therapy.

Research Limitations and Future Directions ​

While mRNA vaccines have shown great promise, several challenges remain:

  • Stability: mRNA is inherently unstable, necessitating advanced formulation strategies for effective storage and transport.
  • Immunogenicity: The innate immune response can be both beneficial and detrimental; optimizing the balance is critical for vaccine efficacy.
  • Clinical Evaluation: More extensive clinical trials are needed to fully understand the long-term safety and efficacy of mRNA vaccines in diverse populations.

Future research should focus on:

  • Enhancing the stability and delivery efficiency of mRNA vaccines.
  • Investigating the mechanisms underlying immune responses to optimize vaccine design.
  • Expanding applications beyond infectious diseases to include therapeutic vaccines for cancer and autoimmune diseases.

Overall, the field of mRNA vaccines is rapidly evolving, and ongoing innovations are expected to further improve their effectiveness and applicability.

References ​

  1. Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus. - M N Fleeton;M Chen;P Berglund;G Rhodes;S E Parker;M Murphy;G J Atkins;P Liljeström - The Journal of infectious diseases (2001)
  2. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. - L Alexopoulou;A C Holt;R Medzhitov;R A Flavell - Nature (2001)
  3. Kunjin virus replicon vaccine vectors induce protective CD8+ T-cell immunity. - Itaru Anraku;Tracey J Harvey;Richard Linedale;Joy Gardner;David Harrich;Andreas Suhrbier;Alexander A Khromykh - Journal of virology (2002)
  4. Kunjin virus replicon vectors for human immunodeficiency virus vaccine development. - Tracey J Harvey;Itaru Anraku;Richard Linedale;David Harrich;Jason Mackenzie;Andreas Suhrbier;Alexander A Khromykh - Journal of virology (2003)
  5. mRNA is an endogenous ligand for Toll-like receptor 3. - Katalin Karikó;Houping Ni;John Capodici;Marc Lamphier;Drew Weissman - The Journal of biological chemistry (2004)
  6. Recognition of mRNA cap structures by viral and cellular proteins. - Pierre Fechter;George G Brownlee - The Journal of general virology (2005)
  7. The yin and yang of type I interferon activity in bacterial infection. - Thomas Decker;Mathias Müller;Silvia Stockinger - Nature reviews. Immunology (2005)
  8. Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins. - Ellen R A Van Gulck;Peter Ponsaerts;Leo Heyndrickx;Katleen Vereecken;Filip Moerman;Ann De Roo;Robert Colebunders;Glenn Van den Bosch;Dirk R Van Bockstaele;Viggo F I Van Tendeloo;Sabine Allard;Bernard Verrier;Concepción Marañón;Guillaume Hoeffel;Anne Hosmalin;Zwi N Berneman;Guido Vanham - Blood (2006)
  9. Humoral and cellular immune response to RNA immunization with flavivirus replicons derived from tick-borne encephalitis virus. - Judith H Aberle;Stephan W Aberle;Regina M Kofler;Christian W Mandl - Journal of virology (2005)
  10. High guanine and cytosine content increases mRNA levels in mammalian cells. - Grzegorz Kudla;Leszek Lipinski;Fanny Caffin;Aleksandra Helwak;Maciej Zylicz - PLoS biology (2006)

Literatures Citing This Work ​

  1. Innovative Mucosal Vaccine Formulations Against Influenza A Virus Infections. - Cynthia Calzas;Christophe Chevalier - Frontiers in immunology (2019)
  2. Advances in Vaccines. - Helen H Mao;Shoubai Chao - Advances in biochemical engineering/biotechnology (2020)
  3. Immunological Analysis of a CCHFV mRNA Vaccine Candidate in Mouse Models. - Touraj Aligholipour Farzani;Katalin Földes;Koray Ergünay;Hakan Gurdal;Aliye Bastug;Aykut Ozkul - Vaccines (2019)
  4. Enlisting the mRNA Vaccine Platform to Combat Parasitic Infections. - Leroy Versteeg;Mashal M Almutairi;Peter J Hotez;Jeroen Pollet - Vaccines (2019)
  5. Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens. - Cristina Poveda;Amadeo B Biter;Maria Elena Bottazzi;Ulrich Strych - Vaccines (2019)
  6. Advances in RNA Vaccines for Preventive Indications: A Case Study of A Vaccine Against Rabies. - Nicole Armbruster;Edith Jasny;Benjamin Petsch - Vaccines (2019)
  7. Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins. - Seyed Davoud Jazayeri;Chit Laa Poh - Vaccines (2019)
  8. The Rocky Road From Fed-Batch to Continuous Processing With E. coli. - Julian Kopp;Christoph Slouka;Oliver Spadiut;Christoph Herwig - Frontiers in bioengineering and biotechnology (2019)
  9. Comparison of DNA and mRNA vaccines against cancer. - Zohreh Jahanafrooz;Behzad Baradaran;Jafar Mosafer;Mahmoud Hashemzaei;Tayebeh Rezaei;Ahad Mokhtarzadeh;Michael R Hamblin - Drug discovery today (2020)
  10. Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis. - Camila Dos Santos Meira;Lashitew Gedamu - Microorganisms (2019)

... (343 more literatures)

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