{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:32:48Z","timestamp":1785295968255,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010830","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000}}],"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI146420"],"award-info":[{"award-number":["R01AI146420"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI146101"],"award-info":[{"award-number":["R01AI146101"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008513","name":"Thomas Jefferson University","doi-asserted-by":"publisher","award":["N\/A Start-up funds"],"award-info":[{"award-number":["N\/A Start-up funds"]}],"id":[{"id":"10.13039\/100008513","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["P30CA056036"],"award-info":[{"award-number":["P30CA056036"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long\n                    <jats:italic>in vivo<\/jats:italic>\n                    half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune response, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while resistance to\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    decreased. The diminished resistance to\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform\u2019s true impact on human health.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010830","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T13:42:44Z","timestamp":1662126164000},"page":"e1010830","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion"],"prefix":"10.1371","volume":"18","author":[{"given":"Zhen","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Bouteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Herbst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9770-800X","authenticated-orcid":true,"given":"Botond Z.","family":"Igy\u00e1rt\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"ppat.1010830.ref001","article-title":"Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability","author":"K Karik\u00f3","year":"2008","journal-title":"Mol Ther"},{"key":"ppat.1010830.ref002","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1093\/nar\/gkr695","article-title":"Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA","volume":"39","author":"K Karik\u00f3","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010830.ref003","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","article-title":"Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA","volume":"23","author":"K Karik\u00f3","year":"2005","journal-title":"Immunity"},{"key":"ppat.1010830.ref004","doi-asserted-by":"crossref","first-page":"103479","DOI":"10.1016\/j.isci.2021.103479","article-title":"The mRNA-LNP platform\u2019s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory","volume":"24","author":"S Ndeupen","year":"2021","journal-title":"iScience"},{"key":"ppat.1010830.ref005","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1016\/j.immuni.2021.11.001","article-title":"Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses","volume":"54","author":"M-G Alameh","year":"2021","journal-title":"Immunity"},{"key":"ppat.1010830.ref006","doi-asserted-by":"crossref","first-page":"e1010255","DOI":"10.1371\/journal.ppat.1010255","article-title":"Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses","volume":"18","author":"S Ndeupen","year":"2022","journal-title":"PLOS Pathog"},{"key":"ppat.1010830.ref007","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41590-022-01163-9","article-title":"Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine","volume":"23","author":"C Li","year":"2022","journal-title":"Nat Immunol"},{"key":"ppat.1010830.ref008","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.coviro.2021.03.008","article-title":"Future considerations for the mRNA-lipid nanoparticle vaccine platform","author":"BZ Igy\u00e1rt\u00f3","year":"2021","journal-title":"Current Opinion in Virology. 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