ArticlePLoS pathogens2021
Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine.PLoS pathogens · 2022Trial
- Charting the Path Forward for HIV Immune-Based Prevention: Contributions of the Division of AIDS at NIAID.Vaccines · 2026Article
- CD8+ T cells cross-restricted by HLA-B*57 and HLA-E*01 recognize HIV Gag with different functional profiles.JCI insight · 2026Article
- Anti-IL-15 treatment reduces acute lentivirus inflammation and signaling in the brain.Cell reports. Medicine · 2026Article
- Skeletal muscle as a dynamic immunological niche for vaccination.Frontiers in immunology · 2026Review
- Accelerating Innovation: Advancing Opportunities in HIV Vaccine Development.Current HIV research · 2026Review
- Glycoprotein L-deleted single-cycle rhesus cytomegalovirus vectors elicit MHC-E-restricted CD8+ T cells that protect against SIV.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Can Humanized Immune System Mouse and Rat Models Accelerate the Development of Cytomegalovirus-Based Vaccines Against Infectious Diseases and Cancers?International journal of molecular sciences · 2025Review
- Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine.Vaccines · 2025Review
- HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies.Immunological reviews · 2025Review
- Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.Nature communications · 2024Article
- Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjögren's disease.Communications biology · 2024Article
- Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects.Viruses · 2024Review
- Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIV-workshop report.NPJ vaccines · 2024Article
- Viral escape mutations do not account for non-protection from SIVmac239 challenge in RhCMV/SIV vaccinated rhesus macaques.Frontiers in immunology · 2024Article
- Functional genomic analysis of the 68-1 RhCMV-Frontiers in immunology · 2024Article
- Programming cytomegalovirus as an HIV vaccine.Trends in immunology · 2023Review
- Late gene expression-deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV.JCI insight · 2023Article
- Rapid transient and longer-lasting innate cytokine changes associated with adaptive immunity after repeated SARS-CoV-2 BNT162b2 mRNA vaccinations.Frontiers in immunology · 2023Article
- Alternative splicing and genetic variation of mhc-e: implications for rhesus cytomegalovirus-based vaccines.Communications biology · 2022Article
Corrections and comments
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Authors and funding
38 authors at 8 institutions in 2 countries.
Funding
Abstract
Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68-1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68-1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68-1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8+ T cells to mediate protection against SIV challenge.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.