{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:05:42Z","timestamp":1793379942345,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007471","name":"Northern Border University","doi-asserted-by":"publisher","award":["NBU-CRP-2026-3770"],"award-info":[{"award-number":["NBU-CRP-2026-3770"]}],"id":[{"id":"10.13039\/501100007471","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NBU-CRP-2026-3770"],"award-info":[{"award-number":["NBU-CRP-2026-3770"]}],"id":[{"id":"https:\/\/ror.org\/03j9tzj20","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Messenger RNA (mRNA) vaccines have emerged as a versatile platform beyond SARS-CoV-2, with expanding applications in infectious diseases and oncology. However, comprehensive evidence synthesis of non-SARS-CoV-2 mRNA vaccines remains limited. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261323500). MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, and WHO ICTRP were systematically searched for studies published between 1 January 2000 and 28 February 2026. Eligible studies included phase I\u2013III clinical trials and in vivo preclinical studies evaluating non-SARS-CoV-2 mRNA vaccines. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2, ROBINS-I, and SYRCLE tools. Findings were synthesized narratively because of substantial heterogeneity. Results: A total of 40 studies met the eligibility criteria and were included in the review, comprising 20 clinical studies and 20 preclinical studies. Advanced clinical programs targeted influenza and respiratory syncytial virus (RSV), with phase III trials displaying seroconversion rates above 70% with good safety profiles. Preliminary phase I studies for HIV, cytomegalovirus, rabies, and personalized cancer mRNA vaccines showed promising humoral and cellular immune responses. Preclinical studies showed strong antibody and T-cell responses against malaria, tuberculosis, Group B Streptococcus, and Zika virus. Most adverse events were mild to moderate, while serious vaccine-related adverse events were uncommon. Conclusions: Non-SARS-CoV-2 mRNA vaccines demonstrate substantial translational potential across infectious disease and oncology applications. Although the vaccine candidates have demonstrated promising immunogenicity and safety, most are in the early stages of development. This highlights the need for large trials, long-term safety follow-up and better global representation.<\/jats:p>","DOI":"10.3390\/diseases14070230","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T08:43:57Z","timestamp":1782463437000},"page":"230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Pandemic Innovation to Platform Diversification: A Systematic Review of Clinical and Preclinical Development of Non\u2013SARS-CoV-2 mRNA Vaccines"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5765-4580","authenticated-orcid":false,"given":"Shuaibu Abdullahi","family":"Hudu","sequence":"first","affiliation":[{"name":"Center for Health Research, Northern Border University, Arar 91431, Saudi Arabia"},{"name":"Department of Microbiology, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhannad","family":"Alruwaili","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5526-4041","authenticated-orcid":false,"given":"Mohamed","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0110-2343","authenticated-orcid":false,"given":"Emad A.","family":"Morad","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Zagazig University, Zagazig 44519, Al-Sharqia Governorate, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghusun M.","family":"Alhazimi","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Lab, Northern Border Regional Laboratory, Northern Borders Cluster, Arar 73211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7322-9100","authenticated-orcid":false,"given":"Abdulgafar Olayiwola","family":"Jimoh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/d41586-021-02483-w","article-title":"The tangled history of mRNA vaccines","volume":"597","author":"Dolgin","year":"2021","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrd.2017.243","article-title":"mRNA vaccines a new era in vaccinology","volume":"17","author":"Pardi","year":"2018","journal-title":"Nat. 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