{"doi":"10.4049/jimmunol.1901431","title":"Protective Immune Responses Elicited by Deglycosylated Live-Attenuated Simian Immunodeficiency Virus Vaccine Are Associated with IL-15 Effector Functions","abstract":"Abstract Deglycosylated, live-attenuated SIV vaccines elicited protective immune responses against heterologous SIVsmE543-3, which differs from the vaccine strain SIVmac239 to levels similar to those across HIV-1 clades. Two thirds of the vaccinees contained the chronic SIVsmE543-3 infection (controllers), whereas one third did not (noncontrollers). In this study, we investigated immune correlates of heterologous challenge control in rhesus macaques of Burmese origin. Because depletion of CD8+ cells in the controllers by administration of anti-CD8α Ab abrogated the control of viral replication, CD8+ cells were required for the protective immune response. However, classical SIV-specific CD8+ T cells did not account for the protective immune response in all controllers. Instead, IL-15–responding CD8α+ cells, including CD8+ T and NK cells, were significantly higher in the controllers than those in the noncontrollers, before and after vaccination with deglycosylated SIV. It is well established that IL-15 signal transduction occurs through “trans-presentation” in which IL-15 complexed with IL-15Rα on monocytes, macrophages, and dendritic cells binds to IL-15 Rβ/γ expressed on CD8+ T and NK cells. Accordingly, levels of IL-15 stimulation were strongly affected by the depletion of monocytes from PBMCs, implying key roles of innate immune cells. These results suggest that intrinsic IL-15 responsiveness may dictate the outcome of protective responses and may lead to optimized formulations of future broadly protective HIV vaccines.","journal":"The Journal of Immunology","year":2020,"id":111194,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":529164,"name":"Masayuki Fujino","orcid":null,"position":1,"is_corresponding":false},{"id":528383,"name":"Yohei Saito","orcid":"0000-0001-6564-6628","position":2,"is_corresponding":false},{"id":529165,"name":"Nursarat Ahmed","orcid":null,"position":3,"is_corresponding":false},{"id":528384,"name":"Hirotaka Sato","orcid":"0000-0002-8321-9731","position":4,"is_corresponding":false},{"id":528385,"name":"Chie Sugimoto","orcid":"0000-0002-0488-2931","position":5,"is_corresponding":false},{"id":529166,"name":"Tomotaka Okamura","orcid":null,"position":6,"is_corresponding":false},{"id":528386,"name":"Ken‐Ichi Hanaki","orcid":"0000-0002-0805-384X","position":7,"is_corresponding":false},{"id":528387,"name":"Emi E. Nakayama","orcid":"0000-0002-0477-0980","position":8,"is_corresponding":false},{"id":528388,"name":"Tatsuo Shioda","orcid":"0000-0002-3439-8331","position":9,"is_corresponding":false},{"id":447887,"name":"Kouji Matsushima","orcid":"0000-0003-1056-171X","position":10,"is_corresponding":false},{"id":528389,"name":"Aftab A. Ansari","orcid":"0000-0003-4607-7268","position":11,"is_corresponding":false},{"id":258352,"name":"François Villinger","orcid":"0000-0002-7790-2008","position":12,"is_corresponding":false},{"id":528390,"name":"Kazuyasu Mori","orcid":"0000-0002-1841-6376","position":13,"is_corresponding":false},{"id":528382,"name":"Satoru Watanabe","orcid":"0000-0002-4634-4381","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:13:05.597252Z","pmid":"32747501","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":[]}