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

A Comprehensive Review of mRNA Vaccines.

Literature Information

DOI	10.3390/ijms24032700
PMID	36769023
Journal	International journal of molecular sciences
Impact Factor	4.9
JCR Quartile	Q1
Publication Year	2023
Times Cited	152
Keywords	PEGylated lipids, acceptance, adjuvants, antigen presentation, cationic lipids
Literature Type	Journal Article, Review
ISSN	1422-0067
Issue	24(3)
Authors	Vrinda Gote, Pradeep Kumar Bolla, Nagavendra Kommineni, Arun Butreddy, Pavan Kumar Nukala, Sushesh Srivatsa Palakurthi, Wahid Khan

TL;DR

This review highlights the transformative role of mRNA vaccines, particularly during the COVID-19 pandemic, showcasing their advantages in potency, safety, and rapid development facilitated by advancements in nanotechnology for delivery systems. It provides a comprehensive overview of mRNA structure, immune response mechanisms, lipid nanoparticles, manufacturing processes, and future innovations, underscoring the potential of mRNA vaccines in modern medicine.

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PEGylated lipids · acceptance · adjuvants · antigen presentation · cationic lipids

Abstract

mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. These vaccines have progressed from being a mere curiosity to emerging as COVID-19 pandemic vaccine front-runners. The advancements in the field of nanotechnology for developing delivery vehicles for mRNA vaccines are highly significant. In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological function of immunity induction, lipid nanoparticles (LNPs), and the upstream, downstream, and formulation process of mRNA vaccine manufacturing. Additionally, mRNA vaccines in clinical trials are also described. A deep dive into the future perspectives of mRNA vaccines, such as its freeze-drying, delivery systems, and LNPs targeting antigen-presenting cells and dendritic cells, are also summarized.

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Primary Questions Addressed

1. What are the specific advancements in nanotechnology that enhance the delivery of mRNA vaccines?
2. How do lipid nanoparticles (LNPs) improve the stability and efficacy of mRNA vaccines compared to traditional vaccine delivery methods?
3. What challenges remain in the manufacturing process of mRNA vaccines, and how might they be addressed in future developments?
4. In what ways can mRNA vaccines be adapted for use against diseases other than COVID-19?
5. What are the potential implications of freeze-drying mRNA vaccines for global vaccination efforts and storage logistics?

Key Findings

Research Background and Purpose

mRNA vaccines have emerged as a significant advancement in vaccine technology, offering a powerful alternative to traditional vaccines due to their high potency, safety, rapid clinical development, and potential for low-cost manufacturing. This review comprehensively examines the structure, function, and production of mRNA vaccines, highlighting their application during the COVID-19 pandemic and their future potential in combating infectious diseases and cancer.

Main Methods/Materials/Experimental Design

The review outlines several key components of mRNA vaccine technology, focusing on:

1. mRNA Structure: Discusses the importance of the 5' cap, untranslated regions (UTRs), open reading frames (ORF), and poly(A) tails in stabilizing mRNA and facilitating protein translation.
2. Lipid Nanoparticles (LNPs): These are critical for mRNA delivery, providing protection against degradation and enhancing cellular uptake. The review details the components of LNPs, including cationic and ionizable lipids, helper lipids, and PEGylated lipids.

The manufacturing process of mRNA vaccines is structured into three phases:

• Upstream Production: Involves in vitro transcription (IVT) of mRNA from a plasmid template.
• Downstream Purification: Includes various chromatography techniques to isolate and purify mRNA.
• Formulation: Involves mixing mRNA with lipids to form LNPs.

Key Results and Findings

• mRNA vaccines have shown remarkable efficacy in clinical trials, particularly during the COVID-19 pandemic, with Pfizer-BioNTech and Moderna leading the way.
• Advances in LNP technology have improved the delivery and stability of mRNA vaccines, facilitating their rapid deployment.
• Ongoing clinical trials are exploring mRNA vaccines for various infectious diseases and cancers, demonstrating their versatility.

Main Conclusions/Significance/Innovation

The review concludes that mRNA vaccines represent a transformative approach to vaccination, with the potential to address various infectious diseases and cancers effectively. The rapid development and deployment of mRNA vaccines during the COVID-19 pandemic have validated this technology, leading to increased interest in further applications. Future directions include enhancing the stability and delivery of mRNA vaccines, particularly in low-resource settings.

Research Limitations and Future Directions

• Safety and Efficacy: While mRNA vaccines have generally shown favorable safety profiles, there are concerns regarding allergic reactions and the long-term effects of novel components.
• Vaccine Acceptance: Public skepticism and misinformation about vaccines can hinder uptake, necessitating efforts to improve education and trust.
• Access to Vaccines: The need for cold-chain storage presents challenges for distribution, particularly in low-income countries. Research into thermostable mRNA vaccines is critical.

Future research should focus on optimizing mRNA vaccine formulations, exploring alternative delivery systems, and addressing the challenges of vaccine acceptance and accessibility to ensure widespread immunization.

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Literatures Citing This Work

1. Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies. - Pia Gattinger;Anna Ohradanova-Repic;Rudolf Valenta - International journal of molecular sciences (2023)
2. Applications of advances in mRNA-based platforms as therapeutics and diagnostics in reproductive technologies. - Wjdan S Bafleh;Haia M R Abdulsamad;Sally M Al-Qaraghuli;Riwa Y El Khatib;Rawdah Taha Elbahrawi;Azhar Mohamud Abdukadir;Shaima M Alsawae;Zakia Dimassi;Hamdan Hamdan;Junaid Kashir - Frontiers in cell and developmental biology (2023)
3. Recent Advancement in mRNA Vaccine Development and Applications. - Nojoud Al Fayez;Majed S Nassar;Abdullah A Alshehri;Meshal K Alnefaie;Fahad A Almughem;Bayan Y Alshehri;Abdullah O Alawad;Essam A Tawfik - Pharmaceutics (2023)
4. Crimean-Congo Hemorrhagic Fever Virus: Progress in Vaccine Development. - Aykut Ozdarendeli - Diagnostics (Basel, Switzerland) (2023)
5. Protection against Severe Illness versus Immunity-Redefining Vaccine Effectiveness in the Aftermath of COVID-19. - Renuka Roche;Nouha H Odeh;Abhay U Andar;Mohan E Tulapurkar;Joseph A Roche - Microorganisms (2023)
6. Liquid Chromatography Methods for Analysis of mRNA Poly(A) Tail Length and Heterogeneity. - Martin Gilar;Catalin Doneanu;Maissa M Gaye - Analytical chemistry (2023)
7. Updated Considerations for the Immunopharmacological Aspects of the "Talented mRNA Vaccines". - Cristiana Perrotta;Claudio Fenizia;Carla Carnovale;Marco Pozzi;Daria Trabattoni;Davide Cervia;Emilio Clementi - Vaccines (2023)
8. The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment. - Xiangyang Ren;Danyang Su;Doudou Shi;Xiaohong Xiang - Frontiers in bioengineering and biotechnology (2023)
9. In Vitro Transcribed RNA-Based Platform Vaccines: Past, Present, and Future. - Alexey D Perenkov;Alena D Sergeeva;Maria V Vedunova;Dmitri V Krysko - Vaccines (2023)
10. mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents. - Sandro Roier;Vidya Mangala Prasad;Monica M McNeal;Kelly K Lee;Benjamin Petsch;Susanne Rauch - NPJ vaccines (2023)

... (142 more literatures)

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