ArticleVaccine2009
TLR9 agonist, but not TLR7/8, functions as an adjuvant to diminish FI-RSV vaccine-enhanced disease, while either agonist used as therapy during primary RSV infection increases disease severity.
Article in Vaccine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Neonatal BCG Vaccination Influences Cytokine Responses to Toll-like Receptor Ligands and Heterologous Antigens.The Journal of infectious diseases · 2018Trial
- The mRNA-based RSV vaccine mRNA-1345 induces robust and durable CD4Science advances · 2026Article
- Review
- The emerging role of TLR7-mediated signaling in respiratory viral infections and autoimmune diseases.Cellular and molecular life sciences : CMLS · 2026Review
- Review
- Immunogenicity of Recombinant Lipid-Based Nanoparticle Vaccines: Danger Signal vs. Helping Hand.Pharmaceutics · 2023Review
- Unmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses.Nature communications · 2023Article
- The effect of Toll-like receptor agonists on the immunogenicity of MVA-SARS-2-S vaccine after intranasal administration in mice.Frontiers in cellular and infection microbiology · 2023Article
- A third dose of the unmodified COVID-19 mRNA vaccine CVnCoV enhances quality and quantity of immune responses.Molecular therapy. Methods & clinical development · 2022Article
- Early innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes.Journal of biomedical science · 2022Review
- Vaccine-Associated Enhanced Viral Disease: Implications for Viral Vaccine Development.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Review
- Challenges for the Newborn Immune Response to Respiratory Virus Infection and Vaccination.Vaccines · 2020Review
- COVID-19: Mechanisms of Vaccination and Immunity.Vaccines · 2020Review
- Strategies to Prevent SARS-CoV-2-Mediated Eosinophilic Disease in Association with COVID-19 Vaccination and Infection.International archives of allergy and immunology · 2020Review
- Prefusion RSV F Immunization Elicits Th2-Mediated Lung Pathology in Mice When Formulated With a Th2 (but Not a Th1/Th2-Balanced) Adjuvant Despite Complete Viral Protection.Frontiers in immunology · 2020Article
- Article
- Contribution of Cytokines to Tissue Damage During Human Respiratory Syncytial Virus Infection.Frontiers in immunology · 2019Review
- RSV recombinant candidate vaccine G1F/M2 with CpG as an adjuvant prevents vaccine-associated lung inflammation, which may be associated with the appropriate types of immune memory in spleens and lungs.Human vaccines & immunotherapeutics · 2019Article
- Control of Heterologous Simian Immunodeficiency Virus SIVJournal of virology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Agonists for TLR7, TLR8, and TLR9 have been shown to enhance vaccine immunogenicity. We evaluated the impact of TLR activation on RSV disease in a murine model by administering TLR7/8 and TLR9 agonists during FI-RSV immunization or RSV infection. CpG administered during immunization reduced disease following challenge as evidenced by decreased lung pathology, illness, and cytokines. In marked contrast, TLR7/8 agonist had little impact. To evaluate potential therapeutic use, TLR agonists were administered during primary infection. Although type 2 cytokine responses decreased and type 1 cytokines and MIP-1-alpha/beta increased, both TLR7/8 and TLR9 agonists increased clinical symptoms and pulmonary inflammation when administered during primary infection. Thus, TLR9-induced signaling during FI-RSV immunization reduced vaccine-enhanced disease whereas immunostimulatory properties of TLR agonists enhanced disease severity when used during RSV infection. Immunomodulation elicited by TLR9 agonist confirms the adjuvant potential of TLR agonists during RSV immunization. However, in contrast to work done with HIV-1 vaccines, the inability of TLR7/8 agonist to boost type 1 vaccine-induced RSV immunity demonstrates pathogen-TLR specificity. These data reveal that the timing of administration of immunomodulatory agents is critical. Furthermore, these data underscore that amplification of anti-viral immune responses may result in immunopathology rather than immune-mediated protection.
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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.