{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:41:44Z","timestamp":1785436904780,"version":"3.56.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI124429"],"award-info":[{"award-number":["R01AI124429"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK122401"],"award-info":[{"award-number":["R01DK122401"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,10,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      T cells play an important role in initiating antibody responses by instructive signals of cell-cell contacts and secretion of soluble cytokines as mediators. We investigated the role of the modified soluble E2 (sE2\n                      <jats:sub>F442NYT<\/jats:sub>\n                      ) antigen from hepatitis C virus (HCV) on healthy human peripheral blood mononuclear cell (PBMC)-derived immune cells or immunized mouse cells to understand the mechanisms of immune regulation by the candidate vaccine antigen. HCV E2 and E2\n                      <jats:sub>F442NYT<\/jats:sub>\n                      displayed a role in inducing type 17 T-helper cell (Th17) phenotype, as indicated by interleukin-17 (IL-17) expression and signal transducer and activator of transcription 3 (Stat3) phosphorylation. The spleen cells from sE2-mRNA-lipid nanoparticles (LNPs) or sE2\n                      <jats:sub>F442NYT<\/jats:sub>\n                      -mRNA-LNP-immunized mice exhibited similar IL-17A mRNA levels, and Th17 (CXCR3\n                      <jats:sup>\u2212<\/jats:sup>\n                      CCR6\n                      <jats:sup>+<\/jats:sup>\n                      ) cells in CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD44\n                      <jats:sup>+<\/jats:sup>\n                      spleen cells, supporting both sE2 and modified sE2\n                      <jats:sub>\n                        F442NYT\n                        <jats:sup>-<\/jats:sup>\n                      <\/jats:sub>\n                      induced Th17 polarization. Immunohistochemical and multiplex immunofluorescence imaging studies revealed abundant CD4\n                      <jats:sup>+<\/jats:sup>\n                      CXCR5\n                      <jats:sup>+<\/jats:sup>\n                      T cells co-localized with BCL6 in sE2\n                      <jats:sub>F442NYT<\/jats:sub>\n                      -mRNA-LNP immunized mouse spleen cells than unmodified sE2-mRNA-LNP immunized animals, suggesting sE2\n                      <jats:sub>F442NYT<\/jats:sub>\n                      induces stronger follicular helper T cell generation. We previously demonstrated increased total IgG production and isotype switching from IgG1 to IgG2a and IgG2b in sE2\n                      <jats:sub>442NYT<\/jats:sub>\n                      immunized mice. The stronger B and T cell responses observed from modified sE2\n                      <jats:sub>F442NYT<\/jats:sub>\n                      support the overall\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      outcome of the study toward a higher B helper T cell generation from sE2\n                      <jats:sub>F442NYT<\/jats:sub>\n                      -mRNA-LNP immunization as compared to unmodified sE2-mRNA-LNP.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>The study will help rationalize HCV vaccine antigen selection for an effective immune response. Extension by additional strategies may be useful to direct stronger B helper T cell generation for prolonged vaccine-associated protection.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01355-25","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T12:06:49Z","timestamp":1757074009000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Hepatitis C virus modified\n                    <sub>S<\/sub>\n                    E2\n                    <sub>F442NYT<\/sub>\n                    -mRNA-LNP candidate vaccine promotes helper CXCR5\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1128","volume":"99","author":[{"given":"Yuki","family":"Haga","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01p7jjy08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal 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