ArticleVaccine2019
STING pathway stimulation results in a differentially activated innate immune phenotype associated with low nitric oxide and enhanced antibody titers in young and aged mice.
Article in Vaccine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation.Science advances · 2024Article
- Beet supplementation mitigates post-exercise inflammation.Frontiers in nutrition · 2024Article
- Novel nanoadjuvants balance immune activation with modest inflammation: implications for older adult vaccines.Immunity & ageing : I & A · 2023Article
- "Just right" combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation.Immunity & ageing : I & A · 2023Article
- Serological and Uterine Biomarkers for Detecting Endometritis in Mares.Animals : an open access journal from MDPI · 2023Article
- Shaping Neonatal Immunization by Tuning the Delivery of Synergistic Adjuvants via Nanocarriers.ACS chemical biology · 2022Article
- Article
- Type I Interferon Promotes Humoral Immunity in Viral Vector Vaccination.Journal of virology · 2021Article
- The Promise and Challenges of Cyclic Dinucleotides as Molecular Adjuvants for Vaccine Development.Vaccines · 2021Review
- Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production.Science advances · 2021Article
- Article
- The Age of Cyclic Dinucleotide Vaccine Adjuvants.Vaccines · 2020Review
- The Suppressive Attitude of Inflammatory Monocytes in Antiviral Antibody Responses.Viral immunology · 2020Review
- Polyanhydride Nanoparticles Induce Low Inflammatory Dendritic Cell Activation Resulting in CD8International journal of nanomedicine · 2020Article
- New MoDC-Targeting TNF Fusion Proteins Enhance Cyclic Di-GMP Vaccine Adjuvanticity in Middle-Aged and Aged Mice.Frontiers in immunology · 2020Article
- Combination of STING Pathway Agonist With Saponin Is an Effective Adjuvant in Immunosenescent Mice.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOne of the most concerning public health issues, related to vaccination and disease prevention, is the inability to induce durable immune responses following a single-dose immunization. In this regard, the nature of the inflammatory environment induced by vaccine adjuvants can negatively impact the resulting immune response. To address these concerns, new strategies to vaccine design are needed in order to improve the outcomes of immune responses, particularly in immunologically disadvantaged populations.
methodsComparisons of the scope of innate immune activation induced by TLR agonists versus cyclic dinucleotides (CDNs) was performed. Their effects on the activation characteristics (e.g., metabolism, cytokine secretion) of bone marrow derived dendritic cells (BMDCs) were studied. In addition, the differential effects on in vivo induction of antibody responses were measured.
resultsAs compared to TLR ligands, the stimulation of BMDCs with CDNs induced distinctly different metabolic outcomes. Marked differences were observed in the production of nitric oxide (NO) and the cytokine BAFF. These distinct differences were correlated with improved (i.e., more rapid and persistent) vaccine antibody responses in both aged and young mice.
conclusionsOur results illustrate that the innate immune pathway targeted by adjuvants can critically impact the outcome of the immune response post-vaccination. Specifically, CDN stimulation of APCs induced an activation phenotype that was characterized by decreased innate effector molecule production (e.g., NO) and increased BAFF. This was attributed to the induction of an innate inflammatory environment that enabled the host to make the most of the existing B lymphocyte potential. The use of adjuvants that differentially engage mechanisms of innate immune activation would be particularly advantageous for the generation of robust, single dose vaccines. The results of this study demonstrated that CDNs induced differential innate activation and enhanced vaccine induced antibody responses in both young and aged mice.
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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.