{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:30:29Z","timestamp":1788280229168,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Racing Association (JRA) Livestock Development Promotion Project"},{"name":"Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries, and Food Industry, Japan","award":["26058BC"],"award-info":[{"award-number":["26058BC"]}]},{"name":"NARO, Bio-oriented Technology Research Advancement Institution","award":["16817557"],"award-info":[{"award-number":["16817557"]}]},{"name":"NARO, Bio-oriented Technology Research Advancement Institution","award":["JPJ011937"],"award-info":[{"award-number":["JPJ011937"]}]},{"name":"Scientific Research","award":["JP19KK0172"],"award-info":[{"award-number":["JP19KK0172"]}]},{"name":"Scientific Research","award":["JP22K19232"],"award-info":[{"award-number":["JP22K19232"]}]},{"name":"Scientific Research","award":["JP23K23768"],"award-info":[{"award-number":["JP23K23768"]}]},{"name":"Scientific Research","award":["JP23KK0124"],"award-info":[{"award-number":["JP23KK0124"]}]},{"name":"Scientific Research","award":["JP19K15993"],"award-info":[{"award-number":["JP19K15993"]}]},{"name":"Scientific Research","award":["JP22K15005"],"award-info":[{"award-number":["JP22K15005"]}]},{"name":"Scientific Research","award":["JP24K01918"],"award-info":[{"award-number":["JP24K01918"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627005"],"award-info":[{"award-number":["JP223fa627005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Promotion Fund of Hokkaido University Veterinary Teaching Hospital"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Calves have immature immune systems, hence immunization with vaccines is essential to protect them from infectious diseases. However, immune responses to vaccines vary widely among individuals. Therefore, strategies for enhancing vaccine efficacy are needed, particularly those targeting low responders to vaccines. Probiotics have attracted attention because of their beneficial immunomodulatory effects on the host. Although probiotics may improve calf immunity, their potential to enhance immune responses to vaccines in calves remains unclear. Thus, we investigated whether immune responses to vaccines, especially T-cell responses, are enhanced when calves receive a combination of probiotic supplementation and vaccination. Methods: Calves were divided into three feeding groups, as follows: negative control feed, live bacteria-mixed feed (Zeosapo KB), and Clostridium butyricum-only feed (CB). After weaning, all calves received two doses of a live attenuated hexavalent viral vaccine. T-cell responses to a vaccine antigen were evaluated by measuring the expression levels of lymphocyte activation markers CD25 and CD69, as well as Th1 cytokine production, in peripheral blood mononuclear cell culture assays. Results: CD25 expression significantly increased in CD4+ T cells four weeks after the booster vaccination in the Zeosapo KB- and CB-fed groups. In addition, the CD25+CD69+ cell ratio in CD4+ T cells was increased in these groups. The production of Th1 cytokines in the culture supernatant was also increased in the CB-fed group. Conclusions: This clinical study demonstrates that probiotics activate CD4+ T cells and enhance Th1 cytokine responses in vaccinated calves.<\/jats:p>","DOI":"10.3390\/vaccines13111120","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"1120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhancement of Vaccine-Induced T-Cell Responses by Probiotics in Calves"],"prefix":"10.3390","volume":"13","author":[{"given":"Mari","family":"Ikehata","sequence":"first","affiliation":[{"name":"Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-9732","authenticated-orcid":false,"given":"Tomohiro","family":"Okagawa","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"},{"name":"Business Development Unit, FASMAC Co., Ltd., Atsugi 243-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-1494","authenticated-orcid":false,"given":"Yasuhiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Institute for Vaccine Research and Development, Hokkaido University, Sapporo 001-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-899X","authenticated-orcid":false,"given":"Shiro","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"},{"name":"Veterinary Research Unit, International Institute of Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-640X","authenticated-orcid":false,"given":"Kazuhiko","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"},{"name":"Veterinary Research Unit, International Institute of Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan"},{"name":"International Affairs Office, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3230-7109","authenticated-orcid":false,"given":"Satoru","family":"Konnai","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan"},{"name":"Institute for Vaccine Research and Development, Hokkaido University, Sapporo 001-0021, Japan"},{"name":"Veterinary Research Unit, International Institute of Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan"},{"name":"One Health Research Center, Hokkaido University, Sapporo 060-0818, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/35021239","article-title":"Vaccines against Intracellular Infections Requiring Cellular Immunity","volume":"406","author":"Seder","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature23480","article-title":"A Randomized Synbiotic Trial to Prevent Sepsis among Infants in Rural India","volume":"548","author":"Panigrahi","year":"2017","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kayasaki, F., Okagawa, T., Konnai, S., Kohara, J., Sajiki, Y., Watari, K., Ganbaatar, O., Goto, S., Nakamura, H., and Shimakura, H. 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