{"doi":"10.1128/jvi.01355-25","title":"Hepatitis C virus modified <sub>S</sub> E2 <sub>F442NYT</sub> -mRNA-LNP candidate vaccine promotes helper CXCR5 <sup>+</sup> T cells","abstract":"ABSTRACT 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 F442NYT ) 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 F442NYT 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 F442NYT -mRNA-LNP-immunized mice exhibited similar IL-17A mRNA levels, and Th17 (CXCR3 − CCR6 + ) cells in CD4 + CD44 + spleen cells, supporting both sE2 and modified sE2 F442NYT - induced Th17 polarization. Immunohistochemical and multiplex immunofluorescence imaging studies revealed abundant CD4 + CXCR5 + T cells co-localized with BCL6 in sE2 F442NYT -mRNA-LNP immunized mouse spleen cells than unmodified sE2-mRNA-LNP immunized animals, suggesting sE2 F442NYT 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 442NYT immunized mice. The stronger B and T cell responses observed from modified sE2 F442NYT support the overall in vivo outcome of the study toward a higher B helper T cell generation from sE2 F442NYT -mRNA-LNP immunization as compared to unmodified sE2-mRNA-LNP. IMPORTANCE 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.","journal":"Journal of Virology","year":2025,"id":546672,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1439183,"name":"Preedia Babu E","orcid":null,"position":1,"is_corresponding":false},{"id":773494,"name":"Marzena Swiderska‐Syn","orcid":"0000-0001-7364-0728","position":2,"is_corresponding":false},{"id":901040,"name":"Erin K. Reagan","orcid":"0000-0003-3162-4636","position":3,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":4,"is_corresponding":false},{"id":749600,"name":"Ranjit Ray","orcid":"0000-0001-8813-3446","position":5,"is_corresponding":false},{"id":1039301,"name":"Yuki Haga","orcid":"0000-0002-0070-2091","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:36.567932Z","pmid":"40910688","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}