{"doi":"10.1128/spectrum.03350-23","title":"A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV\n            <sub>SF162P3CN</sub>\n            challenge","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            An effective vaccine for combination antiretroviral therapy (cART)-free virologic control of HIV-1 by enhancing antigen-specific effector-memory CD8\n            <jats:sup>+</jats:sup>\n            T lymphocytes could be useful in controlling the AIDS pandemic. Previously, we demonstrated that a programmed death-1 (PD-1)-based DNA vaccine, pRhPD1-p27, was effective in inducing Gag-p27-specific effector-memory CD8\n            <jats:sup>+</jats:sup>\n            T cells for viremia suppression in rhesus macaques infected with pathogenic SHIV\n            <jats:sub>SF162P3CN</jats:sub>\n            for 2 years. In this follow-up study, we report on two pRhPD1-p27-vaccinated and SHIV\n            <jats:sub>SF162P3CN</jats:sub>\n            -infected macaques that have remained alive to date with undetectable viremia levels and low proviral loads over 6 years in the absence of cART, achieving a state of sustained virologic control. Polyfunctional effector-memory Gag-p27-specific T cells were maintained in these macaques. Moreover, several T cell epitopes found at 6 years post-viral challenge were identical to those induced during the vaccination phase, indicating sustained vaccine-induced memory T cell responses. The viral challenge resulted in\n            <jats:italic>de novo</jats:italic>\n            Nef-specific T cell responses, which were also maintained. These Gag-p27- and Nef-specific T cell responses were stronger than those in some SHIV\n            <jats:sub>SF162P3CN</jats:sub>\n            -infected macaques that showed viremia control after experimental therapy using a tandem bispecific neutralizing antibody. Our findings indicate that the PD-1-based DNA vaccine strategy holds promise as a clinical immunotherapy for long-term HIV-1 suppression.\n          </jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE</jats:title>\n            <jats:p>\n              Efficient strategies for HIV-1 cART-free virologic control are critical for ending the AIDS pandemic. The essential role of effector-memory CD8\n              <jats:sup>+</jats:sup>\n              T cells in controlling viremia and eliminating virus-infected cells has made them a promising target for vaccine development. It has been previously reported that PD-1-based DNA vaccination was effective in inducing polyfunctional effector-memory CD8\n              <jats:sup>+</jats:sup>\n              T cells for AIDS virus control for 2 years in rhesus monkeys. This follow-up study extends the findings and shows that a viremia-free period of over 6 years was detected in two monkeys immunized with PD-1-based DNA vaccine against pathogenic SHIV\n              <jats:sub>SF162P3CN</jats:sub>\n              infection in the absence of antiretroviral therapy. Long-term vaccine-induced memory T cell responses were detected. Our results warrant the clinical trials of PD-1-based DNA vaccines for achieving HIV-1 cART-free virologic control used either alone or in combination with other biomedical interventions.\n            </jats:p>\n          </jats:sec>","journal":"Microbiology Spectrum","year":2023,"id":632157,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"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":1038620,"name":"Yik Chun Wong","orcid":null,"position":1,"is_corresponding":false},{"id":1638554,"name":"Menglong Zhong","orcid":null,"position":2,"is_corresponding":false},{"id":1038062,"name":"Yufei Mo","orcid":"0000-0002-5580-698X","position":3,"is_corresponding":false},{"id":582684,"name":"Bo Li","orcid":"0000-0001-8782-2485","position":4,"is_corresponding":false},{"id":1038061,"name":"Lok Yan Yim","orcid":"0000-0001-7971-4011","position":5,"is_corresponding":false},{"id":801787,"name":"Xin Li","orcid":"0000-0002-8779-125X","position":6,"is_corresponding":false},{"id":1165527,"name":"Wan Liu","orcid":"0000-0002-4276-0062","position":7,"is_corresponding":false},{"id":275299,"name":"Yanhua Du","orcid":"0000-0003-4816-5106","position":8,"is_corresponding":false},{"id":277965,"name":"Hui Wang","orcid":"0000-0002-8549-3398","position":9,"is_corresponding":false},{"id":1638555,"name":"Haoji Zhang","orcid":null,"position":10,"is_corresponding":false},{"id":105632,"name":"Zhiwei Chen","orcid":"0000-0002-4511-2888","position":11,"is_corresponding":false},{"id":1544137,"name":"Xiaoen He","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A follow-up study: 6-year cART-free virologic control of rhesus macaques after PD-1-based DNA vaccination against pathogenic SHIV\n            <sub>SF162P3CN</sub>\n            challenge","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            An effective vaccine for combination antiretroviral therapy (cART)-free virologic control of HIV-1 by enhancing antigen-specific effector-memory CD8\n            <jats:sup>+</jats:sup>\n            T lymphocytes could be useful in controlling the AIDS pandemic. Previously, we demonstrated that a programmed death-1 (PD-1)-based DNA vaccine, pRhPD1-p27, was effective in inducing Gag-p27-specific effector-memory CD8\n            <jats:sup>+</jats:sup>\n            T cells for viremia suppression in rhesus macaques infected with pathogenic SHIV\n            <jats:sub>SF162P3CN</jats:sub>\n            for 2 years. In this follow-up study, we report on two pRhPD1-p27-vaccinated and SHIV\n            <jats:sub>SF162P3CN</jats:sub>\n            -infected macaques that have remained alive to date with undetectable viremia levels and low proviral loads over 6 years in the absence of cART, achieving a state of sustained virologic control. Polyfunctional effector-memory Gag-p27-specific T cells were maintained in these macaques. Moreover, several T cell epitopes found at 6 years post-viral challenge were identical to those induced during the vaccination phase, indicating sustained vaccine-induced memory T cell responses. The viral challenge resulted in\n            <jats:italic>de novo</jats:italic>\n            Nef-specific T cell responses, which were also maintained. These Gag-p27- and Nef-specific T cell responses were stronger than those in some SHIV\n            <jats:sub>SF162P3CN</jats:sub>\n            -infected macaques that showed viremia control after experimental therapy using a tandem bispecific neutralizing antibody. Our findings indicate that the PD-1-based DNA vaccine strategy holds promise as a clinical immunotherapy for long-term HIV-1 suppression.\n          </jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE</jats:title>\n            <jats:p>\n              Efficient strategies for HIV-1 cART-free virologic control are critical for ending the AIDS pandemic. The essential role of effector-memory CD8\n              <jats:sup>+</jats:sup>\n              T cells in controlling viremia and eliminating virus-infected cells has made them a promising target for vaccine development. It has been previously reported that PD-1-based DNA vaccination was effective in inducing polyfunctional effector-memory CD8\n              <jats:sup>+</jats:sup>\n              T cells for AIDS virus control for 2 years in rhesus monkeys. This follow-up study extends the findings and shows that a viremia-free period of over 6 years was detected in two monkeys immunized with PD-1-based DNA vaccine against pathogenic SHIV\n              <jats:sub>SF162P3CN</jats:sub>\n              infection in the absence of antiretroviral therapy. Long-term vaccine-induced memory T cell responses were detected. Our results warrant the clinical trials of PD-1-based DNA vaccines for achieving HIV-1 cART-free virologic control used either alone or in combination with other biomedical interventions.\n            </jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37921496","pmcid":"PMC10715146","openalex_id":"https://openalex.org/W4388290581","authors":[],"funders":[{"funder_name":"Theme-based Research Scheme","grant_id":"T11-706/18-N","title":null},{"funder_name":"Hong Kong Research Grant Council General Research Fund","grant_id":"17121420","title":null},{"funder_name":"Health and Medical Research Fund","grant_id":"17160762","title":null},{"funder_name":"Mega-Projects of National Science Research and National Key R&D Program","grant_id":"2018ZX10731101-002-001 and 2021YFC2301900","title":null},{"funder_name":"深圳市科技创新委员会 | Sanming Project of Medicine in Shenzen Municipality","grant_id":"AR160087","title":null}],"total_grants":5,"fwci":0.7337,"citation_percentile":0.69401177,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1128/spectrum.03350-23","host_type":"journal"},{"url":"https://doi.org/10.1128/spectrum.03350-23","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/spectrum.03350-23","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37921496","host_type":"repository"},{"url":"https://hub.hku.hk/handle/10722/348622","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10715146","host_type":"repository"},{"url":"https://doaj.org/article/7809558ce08e421e9b5fed830a5e72ec","host_type":"repository"},{"url":"http://hub.hku.hk/bitstream/10722/348622/1/content.pdf","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10715146/pdf/spectrum.03350-23.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10715146","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10715146?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["HIV Research and Treatment","Immunotherapy and Immune Responses","Virus-based gene therapy research","Animals","Macaca mulatta","Simian Acquired Immunodeficiency Syndrome","CD8-Positive T-Lymphocytes","Simian Immunodeficiency Virus","Vaccines, DNA","Follow-Up Studies","Programmed Cell Death 1 Receptor","Vaccination","DNA","AIDS Vaccines"],"mesh_terms":["Animals","DNA","Follow-Up Studies","Macaca mulatta","Vaccination","Simian Immunodeficiency Virus","Simian Acquired Immunodeficiency Syndrome","AIDS Vaccines","CD8-Positive T-Lymphocytes","Vaccines, DNA","Programmed Cell Death 1 Receptor","Simian immunodeficiency virus"],"keywords":["Cart","Vaccination","Virology","DNA vaccination","Medicine","Biology","Immunology","Immune system","Immunization","Geography","PD-1","Shiv","Hiv-1/aids","Therapeutic Dna Vaccine","Long-term Therapeutic Efficacy"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T08:52:22.592760Z","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":[]}