{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T17:09:00Z","timestamp":1763831340131,"version":"3.37.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"DOI":"10.13039\/100000738","name":"Veterans Affairs","doi-asserted-by":"publisher","award":["BX000207"],"award-info":[{"award-number":["BX000207"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015515","name":"University of Iowa Carver College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015515","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32AI343"],"award-info":[{"award-number":["5T32AI343"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Live attenuated vaccines alter immune functions and are associated with beneficial outcomes. We previously demonstrated that live attenuated yellow fever virus (YFV) vaccine (LA-YF-Vax) dampens T-cell receptor (TCR) signaling in vitro via an RNA-based mechanism. We examined study participants before and after LA-YF-Vax to assess TCR-mediated functions in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Serum samples and peripheral blood mononuclear cells (PBMCs) were obtained before and after LA-YF-Vax (with or without additional vaccines) or quadrivalent influenza vaccine. TCR-mediated activation was determined by interleukin 2 release or phosphorylation of the lymphocyte-specific Src kinase. TCR-regulating phosphatase (protein tyrosine phosphatase receptor type E [PTPRE]) expression was also measured.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared with prevaccination findings, LA-YF-Vax recipient PBMCs demonstrated transient reduction in interleukin 2 release after TCR stimulation and PTPRE levels, unlike in control participants who received quadrivalent influenza vaccine. YFV was detected in 8 of 14 participants after LA-YF-Vax. After incubation of healthy donor PBMCs in serum-derived extracellular vesicles prepared from LA-YF-Vax recipients, TCR signaling and PTPRE levels were reduced after vaccination, even in participants without detectable YFV RNA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>LA-YF-Vax reduces TCR functions and PTPRE levels after vaccination. Extracellular vesicles from serum recapitulated this effect in healthy cells. This likely contributes to the reduced immunogenicity for heterologous vaccines after LA-YF-Vax administration. Identification of specific immune mechanisms related to vaccines should contribute to understanding of the \u201coff-target,\u201d beneficial effects of live vaccines.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad086","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T23:38:07Z","timestamp":1680219487000},"page":"786-794","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of \u201cOff-Target\u201d Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine"],"prefix":"10.1093","volume":"229","author":[{"given":"J","family":"Xiang","sequence":"first","affiliation":[{"name":"Iowa City Department of Veterans Affairs Healthcare System, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q","family":"Chang","sequence":"additional","affiliation":[{"name":"Iowa City Department of Veterans Affairs Healthcare System, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J H","family":"McLinden","sequence":"additional","affiliation":[{"name":"Iowa City Department of Veterans Affairs Healthcare System, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration , Silver Spring, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J L","family":"Welch","sequence":"additional","affiliation":[{"name":"Iowa City Department of Veterans Affairs Healthcare System, University of Iowa , Iowa City, Iowa , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T M","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Iowa City Department of Veterans Affairs Healthcare 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