{"doi":"10.1016/j.ebiom.2025.106070","title":"PD-1 blockade enhances functional vaccine-induced HIV-1 CD8+ T-cell responses in PWH receiving early ART","abstract":null,"journal":"eBioMedicine","year":2026,"id":638083,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1657084,"name":"Alba Ruiz","orcid":null,"position":1,"is_corresponding":false},{"id":369703,"name":"Dan Ouchi","orcid":"0000-0002-8630-152X","position":2,"is_corresponding":false},{"id":1657088,"name":"Esther Jimenez-Moyano","orcid":null,"position":3,"is_corresponding":false},{"id":1081922,"name":"Ruth Peña","orcid":"0000-0002-3173-116X","position":4,"is_corresponding":false},{"id":404601,"name":"Oscar Blanch-Lombarte","orcid":"0000-0002-8317-7535","position":5,"is_corresponding":false},{"id":866703,"name":"Dan Gorman","orcid":null,"position":6,"is_corresponding":false},{"id":1657093,"name":"Richard Barnard","orcid":null,"position":7,"is_corresponding":false},{"id":291824,"name":"Tomáš Hanke","orcid":"0000-0002-6076-9546","position":8,"is_corresponding":false},{"id":97919,"name":"Bonaventura Clotet","orcid":"0000-0003-3232-4598","position":9,"is_corresponding":false},{"id":263023,"name":"Bonnie J. Howell","orcid":"0000-0002-5915-9943","position":10,"is_corresponding":false},{"id":97914,"name":"Christian Brander","orcid":"0000-0002-0548-5778","position":11,"is_corresponding":false},{"id":97904,"name":"Beatriz Mothe","orcid":"0000-0001-9975-407X","position":12,"is_corresponding":false},{"id":404602,"name":"Júlia G. Prado","orcid":"0000-0002-5439-4645","position":13,"is_corresponding":false},{"id":1657083,"name":"Miguel Marin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"PD-1 blockade enhances functional vaccine-induced HIV-1 CD8+ T-cell responses in PWH receiving early ART","abstract":"Background Immunotherapeutic strategies combining Immune checkpoint blockade (ICB) and therapeutic T-cell vaccination hold promise to enhance HIV-1 remission in people with HIV (PWH). While T-cell vaccination alone has shown limited efficacy, ICB may potentiate vaccine-induced T-cell responses. We investigate the functional impact of ICB on vaccine-induced HIV-1-specific CD8 + T-cell responses using relevant samples from PWH receiving early ART and T-cell vaccination. Methods We conducted comparative laboratory studies on PD-1 and TIM-3 blockade using biological samples from PWH on early ART and T-cell vaccination (Etvac), or without vaccination (Et) from the BCN01 trial, a phase I non-randomised, multicenter therapeutic HIV-1 vaccine study. Also, we included samples from PWH receiving ART during chronic infection stages (Chro). We assessed and characterised vaccine-induced and HIV-1-specific CD8 + T-cell responses using in vitro peptide stimulation, flow cytometry and multiplex assays. We also investigated correlates of response to ICB. Findings PD-1 blockade significantly increased vaccine-induced HIV-1-specific CD8 + T cell responses in the Etvac group, primarily absent prior vaccination, with no effect from TIM-3 blockade. No effect was found in the Et group for any of the tested conditions, while Chro under PD-1 or PD-1/TIM-3 blockade elicited an increase in HIV-1-specific CD8 + T cells. Differentially, vaccine-induced HIV-1-specific CD8 + T cells in response to PD-1 blockade co-express functional markers, sharing a unique profile of soluble molecules. Furthermore, PD-1 expression on CD8 + T cells correlated with in vitro response to PD-1 blockade in Etvac, suggesting its potential as a biomarker in vaccine studies. Interpretation PD-1 blockade enhances functional vaccine-induced HIV-1-specific CD8 + T-cell responses in PWH during early treatment, supporting further clinical investigation into combining ICB to improve therapeutic T-cell vaccine efficacy in PWH. Funding This research was partially supported by grants from the National Health Institute Carlos III (PI17/00164), Merck Sharp & Dohme LLC (MSD LKR 155762), a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and the Catalan Government with the European Social Fund (AGAUR-FI_B 00582 and 2021 SGR 00452).","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41370970","pmcid":"PMC12752766","openalex_id":"https://openalex.org/W4417274001","authors":[],"funders":[{"funder_name":"Instituto de Salud Carlos III","grant_id":"PI17/00164","title":null},{"funder_name":"European Social Fund Plus","grant_id":"2021 SGR 00452","title":null},{"funder_name":"European Social Fund Plus","grant_id":"AGAUR-FI_B 00582","title":null},{"funder_name":"Merck","grant_id":"MSD LKR 155762","title":null}],"total_grants":4,"fwci":1.8947,"citation_percentile":0.86269941,"influential_citations":0,"citation_trend":[{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1016/j.ebiom.2025.106070","host_type":"journal"},{"url":"https://doi.org/10.1016/j.ebiom.2025.106070","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2352396425005201?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2352396425005201?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41370970","host_type":"repository"},{"url":"https://doaj.org/article/8f1dcf5055ff493eb5d9a077952c1634","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12752766/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12752766","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12752766?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["HIV Research and Treatment","Immunotherapy and Immune Responses","T-cell and B-cell Immunology","Adult","Female","Humans","Male","Middle Aged","AIDS Vaccines","CD8-Positive T-Lymphocytes","Hepatitis A Virus Cellular Receptor 2","HIV Infections","HIV-1","Immune Checkpoint Inhibitors","Programmed Cell Death 1 Receptor","Vaccination"],"mesh_terms":["Hepatitis A Virus Cellular Receptor 2","Immune Checkpoint Inhibitors","Adult","Female","Humans","Male","Middle Aged","Vaccination","HIV-1","HIV Infections","AIDS Vaccines","CD8-Positive T-Lymphocytes","Programmed Cell Death 1 Receptor"],"keywords":["Catalan","Government (linguistics)","Blockade","MEDLINE","Set (abstract data type)","Government regulation","HIV-1","Cd8(+) T Cells","Αpd-1","Combinatorial Immunotherapies","Αtim-3"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T20:05:20.498157Z","pmid":null,"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":[]}