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

Advances in COVID-19 mRNA vaccine development. ​

Literature Information ​

DOI10.1038/s41392-022-00950-y
PMID35322018
JournalSignal transduction and targeted therapy
Impact Factor52.7
JCR QuartileQ1
Publication Year2022
Times Cited240
KeywordsCOVID-19, mRNA vaccine, vaccine development, immune response, public health
Literature TypeJournal Article, Review
ISSN2059-3635
Pages94
Issue7(1)
AuthorsEnyue Fang, Xiaohui Liu, Miao Li, Zelun Zhang, Lifang Song, Baiyu Zhu, Xiaohong Wu, Jingjing Liu, Danhua Zhao, Yuhua Li

TL;DR ​

This review highlights the urgent need for effective COVID-19 vaccination in light of the pandemic's global impact, characterized by over 399 million cases and 5.7 million deaths. It focuses on the advantages of mRNA vaccines, including rapid development and adaptability to variants, while discussing their structural features, delivery systems, and the challenges and future directions in mRNA vaccine technology for infectious diseases.

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COVID-19 · mRNA vaccine · vaccine development · immune response · public health

Abstract ​

To date, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has determined 399,600,607 cases and 5,757,562 deaths worldwide. COVID-19 is a serious threat to human health globally. The World Health Organization (WHO) has declared COVID-19 pandemic a major public health emergency. Vaccination is the most effective and economical intervention for controlling the spread of epidemics, and consequently saving lives and protecting the health of the population. Various techniques have been employed in the development of COVID-19 vaccines. Among these, the COVID-19 messenger RNA (mRNA) vaccine has been drawing increasing attention owing to its great application prospects and advantages, which include short development cycle, easy industrialization, simple production process, flexibility to respond to new variants, and the capacity to induce better immune response. This review summarizes current knowledge on the structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials and real-world data of COVID-19 mRNA vaccines as well as mRNA technology. Current challenges and future directions in the development of preventive mRNA vaccines for major infectious diseases are also discussed.

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Primary Questions Addressed ​

  1. What are the latest breakthroughs in the design of mRNA vaccine antigens for COVID-19?
  2. How do mRNA vaccines compare to traditional vaccine technologies in terms of safety and efficacy?
  3. What role does mRNA vaccine technology play in addressing emerging variants of SARS-CoV-2?
  4. What are the implications of mRNA vaccine development for future vaccine strategies against other infectious diseases?
  5. How can industrialization challenges in mRNA vaccine production be overcome to enhance global vaccination efforts?

Key Findings ​

Research Background and Objectives ​

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global health impacts, with millions of cases and deaths reported. Vaccination is considered the most effective strategy to control the spread of the virus. This review focuses on the advancements in the development of COVID-19 mRNA vaccines, which have garnered attention due to their rapid development, ability to induce strong immune responses, and adaptability to emerging variants.

Main Methods/Materials/Experimental Design ​

The review summarizes various aspects of mRNA vaccine technology, including:

  • Antigen Design Strategies: The design of mRNA vaccines primarily targets the spike (S) protein of SARS-CoV-2, with modifications such as the 2P mutation to stabilize the prefusion conformation.
  • Delivery Systems: Lipid nanoparticles (LNPs) are commonly used to deliver mRNA, enhancing stability and facilitating cellular uptake. The review discusses different lipid formulations and their roles in mRNA delivery.
  • Production Process: The mRNA is synthesized in vitro, purified, and formulated into LNPs for vaccination. The production cycle is streamlined to ensure rapid availability of vaccines.
  • Quality Control: Ensuring the safety and efficacy of mRNA vaccines involves stringent quality control measures throughout the production process.
Mermaid diagram

Key Results and Findings ​

  1. Vaccine Efficacy: mRNA vaccines such as BNT162b2 and mRNA-1273 have shown high efficacy in preventing COVID-19, including severe cases and hospitalization.
  2. Immunogenicity: The mRNA vaccines induce robust humoral and cellular immune responses, providing protection against multiple variants of SARS-CoV-2.
  3. Safety Profile: Adverse effects are generally mild to moderate, with rare instances of myocarditis and anaphylaxis noted, particularly in specific populations.

Main Conclusions/Significance/Innovation ​

The review highlights the transformative role of mRNA technology in vaccine development, emphasizing its rapid deployment during the COVID-19 pandemic. The adaptability of mRNA vaccines to target new variants presents a significant advancement in public health response strategies. Future directions include improving vaccine stability, exploring alternative delivery systems, and expanding mRNA technology applications to other infectious diseases and therapeutic areas.

Research Limitations and Future Directions ​

  • Storage Challenges: The requirement for ultra-low temperature storage of mRNA vaccines poses logistical challenges for distribution.
  • Long-term Immunity: Further studies are needed to assess the durability of immune responses and the necessity for booster doses.
  • Expanding Applications: Future research may focus on applying mRNA technology to other infectious diseases and therapeutic areas beyond COVID-19, leveraging the lessons learned during the pandemic.

This comprehensive review underscores the importance of mRNA vaccine technology in addressing current and future public health challenges.

References ​

  1. Cap 1 Messenger RNA Synthesis with Co-transcriptional CleanCap® Analog by In Vitro Transcription. - Jordana M Henderson;Andrew Ujita;Elizabeth Hill;Sally Yousif-Rosales;Cory Smith;Nicholas Ko;Taylor McReynolds;Charles R Cabral;Julienne R Escamilla-Powers;Michael E Houston - Current protocols (2021)
  2. Foreign nucleic acids as the stimulus to make interferon. - A ISAACS;R A COX;Z ROTEM - Lancet (London, England) (1963)
  3. 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)
  4. A Modified mRNA Vaccine Targeting Immunodominant NS Epitopes Protects Against Dengue Virus Infection in HLA Class I Transgenic Mice. - Claude Roth;Tineke Cantaert;Chloé Colas;Matthieu Prot;Isabelle Casadémont;Laurine Levillayer;Jessie Thalmensi;Pierre Langlade-Demoyen;Christiane Gerke;Kapil Bahl;Giuseppe Ciaramella;Etienne Simon-Loriere;Anavaj Sakuntabhai - Frontiers in immunology (2019)
  5. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. - Daniel Wrapp;Nianshuang Wang;Kizzmekia S Corbett;Jory A Goldsmith;Ching-Lin Hsieh;Olubukola Abiona;Barney S Graham;Jason S McLellan - Science (New York, N.Y.) (2020)
  6. Model-driven engineering of gene expression from RNA replicons. - Jacob Beal;Tyler E Wagner;Tasuku Kitada;Odisse Azizgolshani;Jordan Moberg Parker;Douglas Densmore;Ron Weiss - ACS synthetic biology (2015)
  7. BNT162b2 mRNA COVID-19 Vaccine: First Approval. - Yvette N Lamb - Drugs (2021)
  8. Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar. - Hiam Chemaitelly;Patrick Tang;Mohammad R Hasan;Sawsan AlMukdad;Hadi M Yassine;Fatiha M Benslimane;Hebah A Al Khatib;Peter Coyle;Houssein H Ayoub;Zaina Al Kanaani;Einas Al Kuwari;Andrew Jeremijenko;Anvar H Kaleeckal;Ali N Latif;Riyazuddin M Shaik;Hanan F Abdul Rahim;Gheyath K Nasrallah;Mohamed G Al Kuwari;Hamad E Al Romaihi;Adeel A Butt;Mohamed H Al-Thani;Abdullatif Al Khal;Roberto Bertollini;Laith J Abu-Raddad - The New England journal of medicine (2021)
  9. Myocarditis after Covid-19 Vaccination in a Large Health Care Organization. - Guy Witberg;Noam Barda;Sara Hoss;Ilan Richter;Maya Wiessman;Yaron Aviv;Tzlil Grinberg;Oren Auster;Noa Dagan;Ran D Balicer;Ran Kornowski - The New England journal of medicine (2021)
  10. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. - Katalin Karikó;Michael Buckstein;Houping Ni;Drew Weissman - Immunity (2005)

Literatures Citing This Work ​

  1. COVID-19 vaccine development: milestones, lessons and prospects. - Maochen Li;Han Wang;Lili Tian;Zehan Pang;Qingkun Yang;Tianqi Huang;Junfen Fan;Lihua Song;Yigang Tong;Huahao Fan - Signal transduction and targeted therapy (2022)
  2. Development of DNA Vaccine Candidate against SARS-CoV-2. - Xingyun Wang;Nino Rcheulishvili;Jie Cai;Cong Liu;Fengfei Xie;Xing Hu;Nuo Yang;Mengqi Hou;Dimitri Papukashvili;Yunjiao He;Peng George Wang - Viruses (2022)
  3. Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response. - Mark B Carascal;Rance Derrick N Pavon;Windell L Rivera - Frontiers in immunology (2022)
  4. Advances in nanotechnology application in biosafety materials: A crucial response to COVID-19 pandemic. - Rasmi V Morajkar;Akhil S Kumar;Rohan K Kunkalekar;Amit A Vernekar - Biosafety and health (2022)
  5. Lipid nanoparticles in the development of mRNA vaccines for COVID-19. - Barnabas Wilson;Kannoth Mukundan Geetha - Journal of drug delivery science and technology (2022)
  6. Message in a bottle: mRNA vaccination for influenza. - Jessica R Shartouny;Anice C Lowen - The Journal of general virology (2022)
  7. Current Evidence in SARS-CoV-2 mRNA Vaccines and Post-Vaccination Adverse Reports: Knowns and Unknowns. - Dimitra S Mouliou;Efthimios Dardiotis - Diagnostics (Basel, Switzerland) (2022)
  8. Clinical and Molecular Characterization of a Rare Case of BNT162b2 mRNA COVID-19 Vaccine-Associated Myositis. - Eli Magen;Sumit Mukherjee;Mahua Bhattacharya;Rajesh Detroja;Eugene Merzon;Idan Blum;Alejandro Livoff;Mark Shlapobersky;Gideon Baum;Ran Talisman;Evgenia Cherniavsky;Amir Dori;Milana Frenkel-Morgenstern - Vaccines (2022)
  9. Meeting the Need for a Discussion of Unmet Medical Need. - Denis Horgan;Bettina Borisch;Bogi Eliasen;Peter Kapitein;Andrew V Biankin;Stefan Gijssels;Michael Zaiac;Marie-Helene Fandel;Jonathan A Lal;Marta Kozaric;Barbara Moss;Ruggero De Maria;Marius Geanta;Frédérique Nowak;Antoni Montserrat-Moliner;Olaf Riess - Healthcare (Basel, Switzerland) (2022)
  10. The Delivery of mRNA Vaccines for Therapeutics. - Nitika;Jiao Wei;Ai-Min Hui - Life (Basel, Switzerland) (2022)

... (230 more literatures)

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