{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:13:53Z","timestamp":1789708433997,"version":"4.0.1"},"reference-count":83,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016958","name":"Office of Research Infrastructure Programs, National Institutes of Health","doi-asserted-by":"publisher","award":["1 K01 OD027058"],"award-info":[{"award-number":["1 K01 OD027058"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>The canine rabies vaccine consists of the whole killed rabies virus and an alum adjuvant. While it is known to provide immunological protection in dogs, its effects on cell-mediated responses remain largely uncharacterized. Here, we analyzed blood and spleen samples from vaccinated dogs to understand adaptive immune responses <jats:italic>ex vivo<\/jats:italic> following restimulation with rabies vaccine antigens. Our results showed that recombinant rabies virus glycoprotein (RABV-G) elicited higher antibody titers and IFN\u03b3 production compared to recombinant rabies virus nucleoprotein (RABV-N). CD4<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> double-positive (DP) T cells proliferate robustly after five days of RABV-G stimulation, which was inhibited by an anti-canine MHC class II blocking antibody. Both RABV-G-specific CD4<jats:sup>+<\/jats:sup> and DP T cells demonstrated a polarized T<jats:sub>H<\/jats:sub>1 phenotype, with minor subsets showing T<jats:sub>H<\/jats:sub>1\/T<jats:sub>H<\/jats:sub>17 hybrid and pathogenic T<jats:sub>H<\/jats:sub>1\/T<jats:sub>H<\/jats:sub>17 hybrid cell features. CD4<jats:sup>+<\/jats:sup> T cells were primarily effector memory T cells (T<jats:sub>EM<\/jats:sub>), while DP T cells exhibited a terminally differentiated effector memory phenotype that re-expressed CD45RA (T<jats:sub>EMRA<\/jats:sub>). Both RABV-G-specific CD4<jats:sup>+<\/jats:sup> and DP T cells were detectable up to 1,024 days post-vaccination in spleen samples and their proliferative capacities were unaffected by age. Our results provide the first characterization of canine RABV-G-specific T cell phenotypes in the spleen and blood following rabies vaccination.<\/jats:p>","DOI":"10.1371\/journal.pone.0323823","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T17:33:28Z","timestamp":1747071208000},"page":"e0323823","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rabies vaccination induces a CD4+ TEM and CD4+CD8+ TEMRA TH1 phenotype in dogs"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3882-7276","authenticated-orcid":true,"given":"Haeree P.","family":"Lang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah F.","family":"Almeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc K.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7510-2322","authenticated-orcid":true,"given":"Steven G.","family":"Friedenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"issue":"5","key":"pone.0323823.ref001","doi-asserted-by":"crossref","first-page":"213","DOI":"10.5326\/JAAHA-MS-Canine-Vaccination-Guidelines","article-title":"2022 AAHA canine vaccination guidelines","volume":"58","author":"J Ellis","year":"2022","journal-title":"J Am Anim Hosp Assoc"},{"key":"pone.0323823.ref002","doi-asserted-by":"crossref","first-page":"110630","DOI":"10.1016\/j.vetimm.2023.110630","article-title":"Influence of age and vaccination interval on canine parvovirus, distemper virus, and adenovirus serum antibody titers","volume":"262","author":"SE 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