{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:51:50Z","timestamp":1789829510300,"version":"4.0.1"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>A mRNA vaccine is a type of vaccine that induces an immune response. Antigen-encoding mRNA is delivered via vaccine carriers into the immune cells, which are produced because of antigen-encoding mRNA translation, a protein. For example, COVID-19 mRNA vaccines produce the spike protein of the COVID-19 virus, whereas for influenza virus, mRNA vaccines target the haemagglutinin protein to treat the flu, and it requires modifications depending on the pandemic or seasonal viruses as it is capable of adapting the immune response, which makes the development of vaccines arduous. The protein molecule promotes an adaptive immune response that eliminates and terminates the corresponding virus or pathogen. There are many challenges to delivering an mRNA vaccine into the body; hence, the encapsulation of the mRNA (usually within lipid nanoparticles) is necessary to protect the mRNA from the body\u2019s surrounding environment. In this review article, we focus mainly on the production, formulation, and stabilization of mRNA vaccines in general, elaborating more on and focusing more on SARS-CoV-2, or COVID-19, and influenza viruses, which have become a major concern as these viruses have turned into life-threatening diseases.<\/jats:p>","DOI":"10.3390\/pathogens13060500","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T06:47:30Z","timestamp":1718174850000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Brief Insights into mRNA Vaccines: Their Successful Production and Nanoformulation for Effective Response against COVID-19 and Their Potential Success for Influenza A and B"],"prefix":"10.3390","volume":"13","author":[{"given":"Amerah","family":"Parveen","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR1 3SD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0781-1127","authenticated-orcid":false,"given":"Amal Ali","family":"Elkordy","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR1 3SD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1021\/acs.molpharmaceut.2c00092","article-title":"A Biopharmaceutical Perspective on Higher-Order Structure and Thermal Stability of mRNA Vaccines","volume":"19","author":"Kloczewiak","year":"2022","journal-title":"Mol. Pharm."},{"key":"ref_2","unstructured":"Pollard, T.D., Earnshaw, W.C., Lippincott-Schwartz, J., and Johnson, G.T. (2017). Protein Synthesis and Folding. Cell Biology, Elsevier. [3rd ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41392-022-01007-w","article-title":"mRNA-based therapeutics: Powerful and versatile tools to combat diseases","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.sbi.2015.11.007","article-title":"Computational modeling of RNA 3D structures and interactions","volume":"37","author":"Dawson","year":"2016","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.xphs.2022.11.001","article-title":"The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case","volume":"112","author":"Blenke","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nbt.3802","article-title":"Overcoming cellular barriers for RNA therapeutics","volume":"35","author":"Dowdy","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10604","DOI":"10.1093\/nar\/gkab764","article-title":"Theoretical basis for stabilizing messenger RNA through secondary structure design","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12943-023-01807-w","article-title":"The use of RNA-based treatments in the field of cancer immunotherapy","volume":"22","author":"Chehelgerdi","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2256422","DOI":"10.1080\/22221751.2023.2256422","article-title":"An mRNA-based broad-spectrum vaccine candidate confers cross-protection against heterosubtypic influenza A viruses","volume":"12","author":"Xiong","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.7150\/ijbs.59233","article-title":"mRNA vaccines for COVID-19: What, why and how","volume":"17","author":"Park","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/1521-4141(200001)30:1<1::AID-IMMU1>3.0.CO;2-#","article-title":"In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies","volume":"30","author":"Hoerr","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jconrel.2022.03.032","article-title":"mRNA vaccines for COVID-19 and diverse diseases","volume":"345","author":"Hussain","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_13","unstructured":"Schlegel-O\u2019Brien, K. (2024, June 05). What Are mRNA vaccines? Advanced Science News 2021. Available online: https:\/\/www.advancedsciencenews.com\/what-are-mrna-vaccines\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.copbio.2021.09.016","article-title":"Principles for designing an optimal mRNA lipid nanoparticle vaccine","volume":"73","author":"Kon","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e31476","DOI":"10.7554\/eLife.31476","article-title":"Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity","volume":"6","author":"Yourik","year":"2017","journal-title":"eLife"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114000","DOI":"10.1016\/j.addr.2021.114000","article-title":"Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic","volume":"179","author":"Jain","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cheng, F., Wang, Y., Bai, Y., Liang, Z., Mao, Q., Liu, D., Wu, X., and Xu, M. (2023). Research Advances on the Stability of mRNA Vaccines. Viruses, 15.","DOI":"10.3390\/v15030668"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17056","DOI":"10.1038\/natrevmats.2017.56","article-title":"Tools for translation: Non-viral materials for therapeutic mRNA delivery","volume":"2","author":"Hajj","year":"2017","journal-title":"Nat. Rev. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.4161\/rna.22269","article-title":"Developing mRNA-vaccine technologies","volume":"9","author":"Schlake","year":"2012","journal-title":"RNA Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1371\/journal.pbio.0040180","article-title":"Zylicz M: High guanine and cytosine content increases mRNA levels in mammalian cells","volume":"4","author":"Kudla","year":"2006","journal-title":"PLoS Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"24075","DOI":"10.1073\/pnas.1908052116","article-title":"mRNA structure regulates protein expression through changes in functional half-life","volume":"116","author":"Mauger","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ouranidis, A., Vavilis, T., Mandala, E., Davidopoulou, C., Stamoula, E., Markopoulou, C.K., Karagianni, A., and Kachrimanis, K. (2021). mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010050"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, M.A. (2019). A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines, 7.","DOI":"10.3390\/vaccines7020037"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41392-022-00950-y","article-title":"Advances in COVID-19 mRNA vaccine development","volume":"7","author":"Fang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1021\/acs.molpharmaceut.2c00010","article-title":"Current Status and Future Perspectives on MRNA Drug Manufacturing","volume":"19","author":"Webb","year":"2022","journal-title":"Mol. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"896958","DOI":"10.3389\/fimmu.2022.896958","article-title":"Recent Advances in the Molecular Design and Delivery Technology of mRNA for Vaccination Against Infectious Diseases","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41541-020-0159-8","article-title":"The promise of mRNA vaccines: A biotech and industrial perspective","volume":"5","author":"Jackson","year":"2020","journal-title":"NPJ Vaccines"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gote, V., Bolla, P.K., Kommineni, N., Butreddy, A., Nukala, P.K., Palakurthi, S.S., and Khan, W. (2023). A Comprehensive Review of mRNA Vaccines. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032700"},{"key":"ref_29","first-page":"71","article-title":"Formulation and Delivery Technologies for mRNA Vaccines","volume":"440","author":"Zeng","year":"2022","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s43586-023-00246-7","article-title":"Nanotechnology-based mRNA vaccines","volume":"3","author":"Chen","year":"2023","journal-title":"Nat. Rev. Methods Prim."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.nantod.2014.04.008","article-title":"Challenges associated with Penetration of Nanoparticles across Cell and Tissue Barriers: A Review of Current Status and Future Prospects","volume":"9","author":"Barua","year":"2014","journal-title":"Nano Today"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7300","DOI":"10.1021\/acs.nanolett.5b02497","article-title":"Optimization of Lipid Nanoparticle Formulations for mRNA Delivery in Vivo with Fractional Factorial and Definitive Screening Designs","volume":"15","author":"Kauffman","year":"2015","journal-title":"Nano Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1039\/D1BM01454D","article-title":"Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA)","volume":"10","author":"Farbiak","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7509","DOI":"10.7150\/thno.77259","article-title":"Lipid nanoparticles for delivery of RNA therapeutics: Current status and the role of in vivo imaging","volume":"12","author":"Lee","year":"2022","journal-title":"Theranostics"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vysochinskaya, V., Shishlyannikov, S., Zabrodskaya, Y., Shmendel, E., Klotchenko, S., Dobrovolskaya, O., Gavrilova, N., Makarova, D., Plotnikova, M., and Elpaeva, E. (2022). Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010008"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.2147\/IJN.S363990","article-title":"Optimization of Lipid Nanoformulations for Effective mRNA Delivery","volume":"17","author":"Chen","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Al Badri, Y.N., Chaw, C.S., and Elkordy, A.A. (2023). Insights into Asymmetric Liposomes as a Potential Intervention for Drug Delivery In-cluding Pulmonary Nanotherapeutics. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010294"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/s41467-020-14527-2","article-title":"Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA","volume":"11","author":"Patel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.ymthe.2019.02.012","article-title":"Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery","volume":"27","author":"Kowalski","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.xphs.2023.11.023","article-title":"Factors Affecting Stability of RNA\u2014Temperature, Length, Concentration, pH, and Buffering Species","volume":"113","author":"Chheda","year":"2024","journal-title":"J. Pharm. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5663","DOI":"10.1038\/s41467-023-41354-y","article-title":"mRNA vaccine quality analysis using RNA sequencing","volume":"14","author":"Gunter","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"120586","DOI":"10.1016\/j.ijpharm.2021.120586","article-title":"mRNA-lipid nanopar. ticle COVID-19 vaccines: Structure and stability","volume":"601","author":"Schoenmaker","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105127","DOI":"10.1016\/j.isci.2022.105127","article-title":"Freeze-drying for the preservation of immunoengineering products","volume":"25","author":"Kommineni","year":"2022","journal-title":"iScience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123319","DOI":"10.1016\/j.ijpharm.2023.123319","article-title":"Assessing the physicochemical stability and intracellular trafficking of mRNA-based COVID-19 vaccines","volume":"644","author":"Fongaro","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41392-023-01579-1","article-title":"mRNA vaccines in disease prevention and treatment","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41586-020-2622-0","article-title":"SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness","volume":"586","author":"Corbett","year":"2020","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1016\/S2666-5247(21)00280-9","article-title":"Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: A randomised, double-blind, placebo-controlled, phase 1 trial","volume":"3","author":"Chen","year":"2022","journal-title":"Lancet Microbe"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9031","DOI":"10.1158\/0008-5472.CAN-10-0699","article-title":"Intranodal Vaccination with Naked Antigen-Encoding RNA Elicits Potent Prophylactic and Therapeutic Antitumoral Immunity","volume":"70","author":"Kreiter","year":"2010","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1126\/science.abm0271","article-title":"A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes","volume":"378","author":"Arevalo","year":"2022","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ymthe.2017.11.017","article-title":"Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses","volume":"26","author":"Vogel","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1038\/s41467-022-32149-8","article-title":"Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses","volume":"13","author":"Pardi","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1016\/j.vaccine.2019.04.074","article-title":"mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials","volume":"37","author":"Feldman","year":"2019","journal-title":"Vaccine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1038\/s41467-018-05482-0","article-title":"Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies","volume":"9","author":"Pardi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_54","unstructured":"(2024, June 05). Emc, 2024. Comirnaty 3 Micrograms\/Dose Concentrate for Dispersion for Injection COVID-19 mRNA Vaccine\u2014Summary of Product Characteristics (SmPC)\u2014(emc). Available online: https:\/\/www.medicines.org.uk\/emc\/product\/14405\/smpc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e807","DOI":"10.1002\/iid3.807","article-title":"Adverse events following COVID-19 mRNA vaccines: A systematic review of cardiovascular complication, thrombosis, and thrombocytopenia","volume":"11","author":"Yasmin","year":"2023","journal-title":"Immun. Inflamm. Dis."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:57:16Z","timestamp":1760108236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":55,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["pathogens13060500"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13060500","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,12]]}}}