ArticleClinical and vaccine immunology : CVI2010
Evaluation of a whole-blood cytokine release assay for use in measuring endotoxin activity of group B Neisseria meningitidis vaccines made from lipid A acylation mutants.
Article in Clinical and vaccine immunology : CVI, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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.
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Auricular Vagus Neuromodulation-A Systematic Review on Quality of Evidence and Clinical Effects.Frontiers in neuroscience · 2021Pooled it
- Raising the alarm: endotoxin contamination in lithium heparin tubes is a threat to cell-based assay reliability.BMC research notes · 2026Article
- Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives.Vaccines · 2025Review
- Harnessing outer membrane vesicles derived fromFrontiers in immunology · 2025Article
- Development of a Monocyte Activation Test for Evaluating Recombinant Hepatitis B Vaccine: A Novel Approach for Pyrogen Assessment.Iranian biomedical journal · 2024Article
- Outer membrane vesicles derived fromFrontiers in immunology · 2024Article
- Mucosal vaccination with outer membrane vesicles derived fromFrontiers in immunology · 2024Article
- Bioengineering Strategies for Developing Vaccines against Respiratory Viral Diseases.Clinical microbiology reviews · 2022Review
- Outer membrane vesicles: moving within the intricate labyrinth of assays that can predict risks of reactogenicity in humans.Human vaccines & immunotherapeutics · 2021Review
- Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding.PLoS pathogens · 2020Article
- Article
- Application of a TLR overexpression cell model in pyrogen detection.Biotechnology and bioengineering · 2019Article
- A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection AgainstFrontiers in cellular and infection microbiology · 2019Article
- Article
- Analysis of IL-6 and IL-1β release in cryopreserved pooled human whole blood stimulated with endotoxin.Innate immunity · 2018Article
- Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis.Clinical and vaccine immunology : CVI · 2016Article
- A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity.Frontiers in immunology · 2016Article
- Measuring Cellular Immunity to Influenza: Methods of Detection, Applications and Challenges.Vaccines · 2015Review
- Production of a Shigella sonnei Vaccine Based on Generalized Modules for Membrane Antigens (GMMA), 1790GAHB.PloS one · 2015Article
- Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial endotoxin interacts with the human immune system via complex immunological pathways. The evaluation of endotoxicity is important in the development of safe vaccines and immunomodulatory therapeutics. The Limulus amebocyte lysate (LAL) assay is generally accepted by the FDA for use for the quantification of lipopolysaccharide (LPS), while the rabbit pyrogen test (RPT) is used to estimate pyrogenicity during early development and production. Other in vitro assays, such as cytokine release assays with human whole blood (WB) or peripheral blood mononuclear cells (PBMCs), have also been used and may better estimate the human immunological response to products containing novel LPS molecules. In this study, WB and PBMC interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) release assays were used to estimate the endotoxic activities of purified LPS and native outer membrane vesicle (NOMV) vaccines derived from wild-type (hexa-acylated lipid A) and genetically detoxified (penta- and tetra-acylated lipid A) group B Neisseria meningitidis. A method for quantification of the differences in endotoxicity observed in the WB and PBMC assays is elucidated. The LAL assay was shown to be relatively insensitive to lipid A variations, and the RPT was less sensitive than the cytokine release assay with WB. The IL-6 and TNF-alpha assays with WB but not the assays with PBMCs distinguished between vaccines containing LPS from penta- and tetra-acylated strains. The high degree of sensitivity of the WB system to LPS variations and the presumed relevance of the use of human tissues to predict toxicity in humans suggest that this assay may be particularly well suited for the safety evaluation of vaccines and therapeutics containing acylation variants of LPS.
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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.