{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T01:21:57Z","timestamp":1778808117944,"version":"3.51.4"},"posted":{"date-parts":[[2026,1,24]]},"group-title":"Immunology","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["3DP2AI144245-01S1"],"award-info":[{"award-number":["3DP2AI144245-01S1"]}]},{"name":"Walder Foundation"},{"name":"Lynn Sage Research Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  mRNA vaccines have transformed prophylactic immunization against infectious diseases as well as therapeutic interventions for cancer. However, their effectiveness against emerging viral variants and a range of malignancies continues to be hindered by suboptimal induction of T cell-mediated immunity. To overcome this limitation, here we developed a polymer-lipid hybrid nanoparticle (PLNP) platform engineered to improve mRNA delivery to antigen-presenting cells (APCs) and to potentiate T cell responses. Relative to conventional mRNA lipid nanoparticle (LNP) vaccines, mRNA PLNP vaccines demonstrated markedly improved lymph node targeting, APC activation, Th1-biased pro-inflammatory cytokine response, and antigen-specific T cell expansion while retaining robust humoral immunity. Remarkably, mRNA-PLNP vaccines generated approximately 50% more antigen-specific CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells than mRNA-LNP vaccines across multiple antigens, including SARS-CoV-2 spike, influenza hemagglutinin, and ovalbumin. In prophylactic applications, mRNA PLNP vaccine provided complete protection against SARS-CoV-2 variants. As a therapeutic approach in a melanoma model, mRNA PLNP vaccination resulted in enhanced tumor control and significantly prolonged survival compared to LNP-based formulations. Collectively, these results establish PLNP as a versatile and broadly applicable platform for augmenting mRNA vaccine efficacy through improved mRNA delivery and T cell priming, offering promising implications for infection prevention and cancer immunotherapy.\n                <\/jats:p>","DOI":"10.64898\/2026.01.22.701138","type":"posted-content","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T04:10:12Z","timestamp":1769314212000},"source":"Crossref","is-referenced-by-count":1,"title":["Polymer-lipid hybrid nanoparticle enhances mRNA delivery and T cell-mediated immunity"],"prefix":"10.64898","author":[{"given":"Xiaolei","family":"Cai","sequence":"first","affiliation":[{"name":"Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 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