{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:42:19Z","timestamp":1792514539822,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development","award":["JP21gm0010008"],"award-info":[{"award-number":["JP21gm0010008"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Agency for Medical Research and Development","award":["JP21fk0108620"],"award-info":[{"award-number":["JP21fk0108620"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Agency for Medical Research and Development","award":["223fa827006h0001"],"award-info":[{"award-number":["223fa827006h0001"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Science and Technology Agency","award":["JPMJPF2022"],"award-info":[{"award-number":["JPMJPF2022"]}],"id":[{"id":"https:\/\/ror.org\/00097mb19","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Education, Culture, Sports, Science and Technology","award":["23K1748"],"award-info":[{"award-number":["23K1748"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Education, Culture, Sports, Science and Technology","award":["21H04962"],"award-info":[{"award-number":["21H04962"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Agency for Medical Research and Development","award":["26fk0108727s0202"],"award-info":[{"award-number":["26fk0108727s0202"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Japan Agency for Medical Research and Development","award":["JP253m0134001"],"award-info":[{"award-number":["JP253m0134001"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The use of lipid nanoparticles (LNPs) to enhance delivery and immunogenicity of mRNA vaccines raises safety concerns due to strong reactogenicity. Developing naked mRNA vaccines, which can be delivered through liquid jet-injection to the skin, may offer a safer alternative, but their immunogenicity has been limited. To address this challenge, we screened clinically relevant adjuvants to enhance the efficacy of N1-methyl-pseudouridine-modified naked mRNA jet-injection vaccines in mouse models. Although many adjuvants showed little or inhibitory effects on inducing humoral or cellular immunity\u2014despite their known ability to potentiate conventional non-mRNA vaccine platforms\u2014we identified a combination of aluminum phosphate and CpG oligonucleotide that substantially enhanced both humoral and cellular immune responses with increased IgG2a\/IgG1 ratio. This adjuvanted naked mRNA vaccine induced IgG2a and cellular immunity at levels comparable to those achieved with LNPs but with lower local and systemic reactogenicity. Mechanistic investigations revealed key roles for type I interferon and interleukin-6 signaling during immunization. Notably, this vaccine formulation in mice virtually eliminated infection by both SARS-CoV-2 and influenza A virus (A\/California\/7\/2009 H1N1) in plaque-forming assays. Collectively, the adjuvanted naked mRNA jet-injection vaccine represents an effective, and safe platform against infectious diseases, with potential for clinic-ready translational applications.<\/jats:p>","DOI":"10.1172\/jci204021","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:00:43Z","timestamp":1792512043000},"source":"Crossref","is-referenced-by-count":0,"title":["Jet-injected combinational adjuvants potentiate naked mRNA vaccines for protection against respiratory viral infections in mice"],"prefix":"10.1172","author":[{"given":"Nan","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Advanced Nanomedical Engineering, Institute of Science Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Advanced Nanomedical Engineering, Institute of Science Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Yasui","sequence":"additional","affiliation":[{"name":"Research Center for Infectious Diseases Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Sano","sequence":"additional","affiliation":[{"name":"Influenza Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Miyakawa","sequence":"additional","affiliation":[{"name":"Influenza Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akimasa","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Faisal","family":"Amiry","sequence":"additional","affiliation":[{"name":"Research Center for Infectious Diseases Medical Sciences, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Advanced Nanomedical Engineering, Institute of Science Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Advanced Nanomedical Engineering, Institute of Science Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Takeda-Miyata","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Pasqualini","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Rutgers Cancer Institute, Newark, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8686-4584","authenticated-orcid":true,"given":"Wadih","family":"Arap","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Rutgers Cancer Institute, Newark, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, Kawasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Influenza Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michinori","family":"Kohara","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Advanced Nanomedical Engineering, Institute of Science Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,20]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/204021\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:00:46Z","timestamp":1792512046000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/204021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":0,"alternative-id":["10.1172\/JCI204021"],"URL":"https:\/\/doi.org\/10.1172\/jci204021","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]}}}