Host factors impacting the innate response in humans to the candidate adjuvants RC529 and monophosphoryl lipid A
| Autor: | John H. Eldridge, David D. Duncan, Lorrie Tiberio, Leah Diane Fletcher |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Lipopolysaccharides Male Adolescent Genotype medicine.medical_treatment Monophosphoryl Lipid A Enzyme-Linked Immunosorbent Assay Receptors Cell Surface Biology Adjuvants Immunologic medicine Humans Allele Alleles Whole blood DNA Primers Sex Characteristics Membrane Glycoproteins Polymorphism Genetic General Veterinary General Immunology and Microbiology Reverse Transcriptase Polymerase Chain Reaction Toll-Like Receptors Public Health Environmental and Occupational Health DNA Middle Aged Flow Cytometry Toll-Like Receptor 4 Kinetics Infectious Diseases Cytokine Lipid A Phenotype Immunology TLR4 Molecular Medicine Cytokines lipids (amino acids peptides and proteins) Female Adjuvant Sex characteristics Signal Transduction |
| Zdroj: | Vaccine. 22(11-12) |
| ISSN: | 0264-410X |
| Popis: | The aim of this study was to determine if certain genotypes might be associated with variable responses to the candidate vaccine adjuvants RC529 and monophosphoryl lipid A (MPL), as well as to bacterial LPS, a structurally similar control stimulus. In this study, the +896 TLR4 polymorphism and selected cytokine polymorphisms were genotyped, and together with the donor sex, these factors were used to model the in vitro cytokine responses to RC529, MPL, and LPS. We show evidence that each of the three stimuli engage human TLR4, that each gave higher responses in men than women, and that TLR4 expression levels in blood monocytes were higher in men than women. From 74 to 92% of the response variation in the whole blood assay was between subjects, yet the multifactorial analyses accounted for only 3-18% of the variation within the study. Potentially there was a sex-dependent TLR4 effect since there was a significant sex-TLR4 interaction term in the multifactorial model for some responses. Since the genotypes we analyzed had such a modest impact in the study, we anticipate that +896 TLR4 genotype and the other factors analyzed in this study have only incremental effects in determining the overall response to TLR4-engaging stimuli. |
| Databáze: | OpenAIRE |
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