ArticlePloS one2016
The TLR4 Agonist Vaccine Adjuvant, GLA-SE, Requires Canonical and Atypical Mechanisms of Action for TH1 Induction.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
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- Cancer vaccines as enablers of immunotherapy.Nature immunology · 2025Review
- A SpA+LukAB vaccine targeting Staphylococcus aureus evasion factors restricts infection in two minipig infection models.NPJ vaccines · 2025Article
- Enhancing vaccine effectiveness in the elderly to counter antibiotic resistance: The potential of adjuvants via pattern recognition receptors.Human vaccines & immunotherapeutics · 2024Review
- Importance of adjuvant selection in tuberculosis vaccine development: Exploring basic mechanisms and clinical implications.Vaccine: X · 2023Review
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- Advances in protein subunit vaccines against tuberculosis.Frontiers in immunology · 2023Review
- New-age vaccine adjuvants, their development, and future perspective.Frontiers in immunology · 2023Review
- Formulated Phospholipids as Non-Canonical TLR4 Agonists.Pharmaceutics · 2022Article
- Advances in Infectious Disease Vaccine Adjuvants.Vaccines · 2022Review
- It Takes a Village: The Multifaceted Immune Response toFrontiers in immunology · 2022Review
- Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments.Frontiers in pharmacology · 2022Review
- Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.BioImpacts : BI · 2022Review
- Review
- Tetravalent Rabies-Vectored Filovirus and Lassa Fever Vaccine Induces Long-term Immunity in Nonhuman Primates.The Journal of infectious diseases · 2021Article
- Review
- Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model.PloS one · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) promotes strong TH1 and balanced IgG1/IgG2 responses to protein vaccine antigens. This enhanced immunity is sufficient to provide protection against many diseases including tuberculosis and leishmaniasis. To better characterize the adjuvant action it is important to understand how the different cytokines and transcription factors contribute to the initiation of immunity. In the present study using T-bet-/- and IL-12-/- mice and a blocking anti-IFNαR1 monoclonal antibody, we define mechanisms of adjuvant activity of GLA-SE. In accordance with previous studies of TLR4 agonist based adjuvants, we found that TH1 induction via GLA-SE was completely dependent upon T-bet, a key transcription factor for IFNγ production and TH1 differentiation. Consistent with this, deficiency of IL-12, a cytokine canonical to TH1 induction, ablated TH1 induction via GLA-SE. Finally we demonstrate that the innate immune response to GLA-SE, including rapid IFNγ production by memory CD8+ T cells and NK cells, was contingent on type I interferon, a cytokine group whose association with TH1 induction is contextual, and that they contributed to the adjuvant activity of GLA-SE.
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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.