Bowen Li, Allen Yujie Jiang, Idris Raji, Caroline Atyeo, Theresa M Raimondo, Akiva G R Gordon, Luke H Rhym, Tahoura Samad, Corina MacIsaac, Jacob Witten, Haseeb Mughal, Taras M Chicz, Yue Xu, Ryan P McNamara, Sangeeta Bhatia, Galit Alter, Robert Langer, Daniel G Anderson
{"title":"Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA.","authors":"Bowen Li, Allen Yujie Jiang, Idris Raji, Caroline Atyeo, Theresa M Raimondo, Akiva G R Gordon, Luke H Rhym, Tahoura Samad, Corina MacIsaac, Jacob Witten, Haseeb Mughal, Taras M Chicz, Yue Xu, Ryan P McNamara, Sangeeta Bhatia, Galit Alter, Robert Langer, Daniel G Anderson","doi":"10.1038/s41551-023-01082-6","DOIUrl":null,"url":null,"abstract":"<p><p>To elicit optimal immune responses, messenger RNA vaccines require intracellular delivery of the mRNA and the careful use of adjuvants. Here we report a multiply adjuvanted mRNA vaccine consisting of lipid nanoparticles encapsulating an mRNA-encoded antigen, optimized for efficient mRNA delivery and for the enhanced activation of innate and adaptive responses. We optimized the vaccine by screening a library of 480 biodegradable ionizable lipids with headgroups adjuvanted with cyclic amines and by adjuvanting the mRNA-encoded antigen by fusing it with a natural adjuvant derived from the C3 complement protein. In mice, intramuscular or intranasal administration of nanoparticles with the lead ionizable lipid and with mRNA encoding for the fusion protein (either the spike protein or the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) increased the titres of antibodies against SARS-CoV-2 tenfold with respect to the vaccine encoding for the unadjuvanted antigen. Multiply adjuvanted mRNA vaccines may improve the efficacy, safety and ease of administration of mRNA-based immunization.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":26.8000,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1038/s41551-023-01082-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 2
Abstract
To elicit optimal immune responses, messenger RNA vaccines require intracellular delivery of the mRNA and the careful use of adjuvants. Here we report a multiply adjuvanted mRNA vaccine consisting of lipid nanoparticles encapsulating an mRNA-encoded antigen, optimized for efficient mRNA delivery and for the enhanced activation of innate and adaptive responses. We optimized the vaccine by screening a library of 480 biodegradable ionizable lipids with headgroups adjuvanted with cyclic amines and by adjuvanting the mRNA-encoded antigen by fusing it with a natural adjuvant derived from the C3 complement protein. In mice, intramuscular or intranasal administration of nanoparticles with the lead ionizable lipid and with mRNA encoding for the fusion protein (either the spike protein or the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) increased the titres of antibodies against SARS-CoV-2 tenfold with respect to the vaccine encoding for the unadjuvanted antigen. Multiply adjuvanted mRNA vaccines may improve the efficacy, safety and ease of administration of mRNA-based immunization.
期刊介绍:
Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.