ArticleJCI insight2021
IL-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Rescuing age-associated vaccine hyporesponsiveness in murine and nonhuman primate models with an immunostimulatory vaccine adjuvant.Human vaccines & immunotherapeutics · 2026Article
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Modulation of pulmonary IL-21 expression during latent TB and M. tuberculosis/SIV coinfection.JCI insight · 2026Article
- Altered Cytokine-Induced STAT3 and STAT5 Activation of Peripheral T Follicular Helper Cells Contributes to Vaccine-Non-Responsiveness in Aging and HIV.Aging cell · 2026Article
- HIV associated immune aging among people living with HIV: implications for long-term antiretroviral therapy and potential HIV cure interventions in sub-Saharan Africa.Frontiers in immunology · 2026Review
- Precision Adjuvant Strategies in Vaccine Development for Substance Use Disorders: Variability and Mechanistic Insights.Pharmaceutics · 2025Review
- T Cell Responses to Influenza Infections in Cattle.Viruses · 2025Review
- Germinal center immune dynamics: challenges for effective vaccination in the elderly.Immunotherapy · 2025Review
- HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.Communications biology · 2024Article
- SHIV-C109p5 NHP induces rapid disease progression in elderly macaques with extensive GI viral replication.Journal of virology · 2024Article
- IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.Aging cell · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Natural aging and HIV infection are associated with chronic low-grade systemic inflammation, immune senescence, and impaired antibody responses to vaccines such as the influenza (flu) vaccine. We investigated the role of IL-21, a CD4+ T follicular helper cell (Tfh) regulator, on flu vaccine antibody response in nonhuman primates (NHPs) in the context of age and controlled SIV mac239 infection. Three doses of the flu vaccine with or without IL-21-IgFc were administered at 3-month intervals in aged SIV+ NHPs following virus suppression with antiretroviral therapy. IL-21-treated animals demonstrated higher day 14-postboost antibody responses, which associated with expanded CD4+ T central memory cells and peripheral Tfh-expressing (pTfh-expressing) T cell immunoreceptor with Ig and ITIM domains (TIGIT), expanded activated memory B cells, and contracted CD11b+ monocytes. Draining lymph node (LN) tissue from IL-21-treated animals revealed direct association between LN follicle Tfh density and frequency of circulating TIGIT+ pTfh cells. We conclude that IL-21 enhances flu vaccine-induced antibody responses in SIV+ aged rhesus macaques (RMs), acting as an adjuvant modulating LN germinal center activity. A strategy to supplement IL-21 in aging could be a valuable addition in the toolbox for improving vaccine responses in an aging HIV+ population.
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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.