{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:07:24Z","timestamp":1783102044363,"version":"3.54.6"},"reference-count":73,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:00:00Z","timestamp":1693612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Jilin Provincial Industrial Innovation Special Project for the New Vaccine Adjuvant Innovation Technology Platform","doi-asserted-by":"publisher","award":["2018C004"],"award-info":[{"award-number":["2018C004"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011789","name":"Jilin Provincial Industrial Innovation Special Project for the New Vaccine Adjuvant Innovation Technology Platform","doi-asserted-by":"publisher","award":["20200708085YY"],"award-info":[{"award-number":["20200708085YY"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011789","name":"Jilin Province Science and Technology Development Plan","doi-asserted-by":"publisher","award":["2018C004"],"award-info":[{"award-number":["2018C004"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011789","name":"Jilin Province Science and Technology Development Plan","doi-asserted-by":"publisher","award":["20200708085YY"],"award-info":[{"award-number":["20200708085YY"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune responses. In this study, we conducted a head-to-head comparison of immune response and safety of inactivated rabies vaccine inoculated via intraperitoneal (IP), intramuscular (IM), subcutaneous (SC) and needle-free injection technology-based intradermal (ID) routes in ICR mice. Immune response was assessed in terms of antigen-specific antibodies, antibody subtypes and neutralizing antibodies for up to 28 weeks. A live rabies virus challenge was also carried out to evaluate vaccine potency. The dynamics of inflammatory cell infiltration at the skin and muscle levels were determined via histopathological examination. The kinetics and distribution of a model antigen were also determined by using in vivo fluorescence imaging. Evidence is presented that the vaccine inoculated via the ID route resulted in the highest antigen-specific antibody and neutralizing antibody titers among all administration routes, while IP and IM routes were comparable, followed by the SC route. Antibody subtype analysis shows that the IP route elicited a Th1-biased immune response, while SC and IM administration elicited a prominent Th2-type immune response. Unexpectedly, the ID route leads to a balanced Th1 and Th2 immune response. In addition, the ID route conferred effective protection against lethal challenge with 40 LD50 of the rabies CVS strain, which was followed by IP and IM routes. Moreover, a one-third dose of the vaccine inoculated via the ID route provided comparable or higher efficacy to a full dose of the vaccine via the other three routes. The superior performance of ID inoculation over other routes is related to longer local retention at injection sites and higher lymphatic drainage. Histopathology examination reveals a transient inflammatory cell infiltration at ID and IM injection sites which peaked at 48 h and 24 h, respectively, after immunization, with all side effects disappearing within one week. These results suggest that needle-free injection technology-based ID inoculation is a promising strategy for rabies vaccination in regard to safety and efficacy.<\/jats:p>","DOI":"10.3390\/ijms241713587","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:14:50Z","timestamp":1693793690000},"page":"13587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Immune Response of Inactivated Rabies Vaccine Inoculated via Intraperitoneal, Intramuscular, Subcutaneous and Needle-Free Injection Technology-Based Intradermal Routes in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7996-2517","authenticated-orcid":false,"given":"Huiting","family":"Zhao","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixuan","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2865-0721","authenticated-orcid":false,"given":"Lijun","family":"Bian","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlai","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Kong","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-5235","authenticated-orcid":false,"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1080\/21645515.2017.1423156","article-title":"Intradermal delivery of a fractional dose of influenza h7n9 split vaccine elicits protective immunity in mice and rats","volume":"14","author":"Zhou","year":"2018","journal-title":"Hum. 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