{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:59:58Z","timestamp":1791230398894,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI158060"],"award-info":[{"award-number":["AI158060"]}]},{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI150091"],"award-info":[{"award-number":["AI150091"]}]},{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI143348"],"award-info":[{"award-number":["AI143348"]}]},{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI147499"],"award-info":[{"award-number":["AI147499"]}]},{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI143326"],"award-info":[{"award-number":["AI143326"]}]},{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI138764"],"award-info":[{"award-number":["AI138764"]}]},{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI124911"],"award-info":[{"award-number":["AI124911"]}]},{"name":"National Institutes of Allergy and Infectious Diseases (NIAID)","award":["AI110902"],"award-info":[{"award-number":["AI110902"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) have emerged as a promising vaccine strategy, especially for COVID-19. While the LNPs protect mRNA from degradation and efficiently deliver the mRNA to antigen-presenting cells, the effect of lipid composition on the immunogenicity and protective efficacy of mRNA\/LNP vaccines is not well characterized. Studies on using the mRNA\/LNP platform for vaccines have largely focused on the nucleic acid cargo with less attention paid to the LNP vehicle. Whether the composition and biophysical properties of LNPs impact vaccine performance remains to be fully elucidated. Methods: In the present study, we used SARS-CoV-2 Spike-mRNA as a prototype vaccine to study the effect of four different LNPs with various lipid compositions. Results: We demonstrate that when the same Spike-mRNA was delivered in the LNP4 formulation based on phospholipid 1,2-dioleoyl-sn-glycero-3-Phosphoethanolamine, it outperformed other LNPs (LNP1, LNP2, and LNP3) that are based on different lipids. Compared to the other three LNPs, LNP4 (i) enhanced the phenotypic and functional maturation of dendritic cells; (ii) induced strong T-cell responses; (iii) increased the secretion of proinflammatory cytokines and pro-follicular T helper (Tfh) cell cytokines; (iv) induced higher neutralization IgG titers; and (v) provided better protection against SARS-CoV-2 infection and COVID-19-like symptoms in the hamster model. Furthermore, we compared LNP-4 with the commercially available LNPs and found it to provide better T-cell immunity against COVID-19 in hamsters. Conclusion: This study suggests mRNA vaccines encapsulated in Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine containing LNPs induced Potent B- and T cell immunity. The mechanisms by which Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine-based LNPs may activate protective B and T cells are discussed.<\/jats:p>","DOI":"10.3390\/vaccines13010047","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T07:40:13Z","timestamp":1736322013000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Spike-Based mRNA Vaccine Encapsulated in Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine Containing Lipid Nanoparticles Induced Potent B- and T-Cell Responses Associated with Protection Against SARS-CoV-2 Infection and COVID-19-like Symptoms in Hamsters"],"prefix":"10.3390","volume":"13","author":[{"given":"Afshana","family":"Quadiri","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3986-890X","authenticated-orcid":false,"given":"Swayam","family":"Prakash","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latifa","family":"Zayou","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha Rajeswari","family":"Dhanushkodi","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7019-2541","authenticated-orcid":false,"given":"Amruth","family":"Chilukuri","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Ryan","sequence":"additional","affiliation":[{"name":"Precision Nanosystems Inc., Vancouver, BC V6P 6T7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Wang","sequence":"additional","affiliation":[{"name":"Precision Nanosystems Inc., Vancouver, BC V6P 6T7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawa","family":"Vahed","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Department of Vaccines and Immunotherapies, TechImmune LLC, University Lab Partners, Irvine, CA 92660, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz A.","family":"Chentoufi","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lbachir","family":"BenMohamed","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Department of Vaccines and Immunotherapies, TechImmune LLC, University Lab Partners, Irvine, CA 92660, USA"},{"name":"Division of Infectious Diseases and Hospitalist Program, Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Institute for Immunology, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023). 2023 WHO Global Vaccine Market Report, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Quadiri, A., Kashif, M., Kalia, I., and Singh, A.P. 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