12 results on '"Bodinham CL"'
Search Results
2. Acute ingestion of resistant starch reduces food intake in healthy adults.
- Author
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Bodinham CL, Frost GS, and Robertson MD
- Published
- 2010
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3. Cynomolgus macaques as a translational model of human immune responses to yellow fever 17D vaccination.
- Author
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Mantel N, Piras-Douce F, Chautard E, Marcos-Lopez E, Bodinham CL, Cosma A, Courtois V, Dhooge N, Gautheron S, Kaufmann SHE, Pizzoferro K, Lewis DJM, Martinon F, Pagnon A, Raynal F, Dereuddre-Bosquet N, and Le Grand R
- Subjects
- Animals, Female, Humans, Male, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, Antibodies, Viral immunology, Immunity, Innate, Systems Biology methods, Vaccination, Yellow Fever prevention & control, Yellow Fever immunology, Yellow Fever virology, Yellow fever virus immunology, Macaca fascicularis, Yellow Fever Vaccine immunology, Models, Animal
- Abstract
The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed the evaluation of the safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a systems biology approach to compare hematological, biochemical, transcriptomic, and innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans but with a slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques [by Day 7[(D7)], but titers > 10 were reached in both species by D14 post-vaccination and were not significantly different by D28 [plaque reduction neutralization assay (PRNT)
50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; P = 0.821]. Changes in neutrophils, NK cells, monocytes, and T- and B-cell frequencies were higher in cynomolgus macaques and persisted for 4 weeks versus less than 2 weeks in humans. Low levels of systemic inflammatory cytokines (IL-1RA, IL-8, MIP-1α, IP-10, MCP-1, or VEGF) were detected in either or both species but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3-D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low-level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques [28% (5/18)] but generally absent in humans [except one participant (5%; 1/20)].IMPORTANCECynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans and suggest a key role for type I IFN., Competing Interests: N.M., FP.-D., E.C., F.R., A.P., S.G., and V.C. are employees of Sanofi and may hold shares and/or stock options in the company. E.M.-L., C.L.B., A.C., N.D., S.H.E.K., K.P., D.J.M.L., F.M., N.D.-B., and R.L.G. declare no competing interest relevant to this report.- Published
- 2024
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4. Systematic Evaluation of Kinetics and Distribution of Muscle and Lymph Node Activation Measured by 18 F-FDG- and 11 C-PBR28-PET/CT Imaging, and Whole Blood and Muscle Transcriptomics After Immunization of Healthy Humans With Adjuvanted and Unadjuvanted Vaccines.
- Author
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Win Z, Weiner Rd J, Listanco A, Patel N, Sharma R, Greenwood A, Maertzdorf J, Mollenkopf HJ, Pizzoferro K, Cole T, Bodinham CL, Kaufmann SHE, Denoel P, Del Giudice G, and Lewis DJM
- Subjects
- Adolescent, Adult, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Cytokines immunology, Female, Humans, Immunization methods, Kinetics, Lymph Nodes immunology, Male, Middle Aged, Muscles immunology, Positron Emission Tomography Computed Tomography methods, Vaccination methods, Vaccines immunology, Young Adult, Adjuvants, Immunologic metabolism, Fluorodeoxyglucose F18 metabolism, Lymph Nodes metabolism, Muscles metabolism, Transcriptome immunology, Vaccines metabolism
- Abstract
Systems vaccinology has been applied to detect signatures of human vaccine induced immunity but its ability, together with high definition in vivo clinical imaging is not established to predict vaccine reactogenicity. Within two European Commission funded high impact programs, BIOVACSAFE and ADITEC, we applied high resolution positron emission tomography/computed tomography (PET/CT) scanning using tissue-specific and non-specific radioligands together with transcriptomic analysis of muscle biopsies in a clinical model systematically and prospectively comparing vaccine-induced immune/inflammatory responses. 109 male participants received a single immunization with licensed preparations of either AS04-adjuvanted hepatitis B virus vaccine (AHBVV); MF59C-adjuvanted (ATIV) or unadjuvanted seasonal trivalent influenza vaccine (STIV); or alum-OMV-meningococcal B protein vaccine (4CMenB), followed by a PET/CT scan (n = 54) or an injection site muscle biopsy (n = 45). Characteristic kinetics was observed with a localized intramuscular focus associated with increased tissue glycolysis at the site of immunization detected by
18 F-fluorodeoxyglucose (FDG) PET/CT, peaking after 1-3 days and strongest and most prolonged after 4CMenB, which correlated with clinical experience. Draining lymph node activation peaked between days 3-5 and was most prominent after ATIV. Well defined uptake of the immune cell-binding radioligand11 C-PBR28 was observed in muscle lesions and draining lymph nodes. Kinetics of muscle gene expression module upregulation reflected those seen previously in preclinical models with a very early (~6hrs) upregulation of monocyte-, TLR- and cytokine/chemokine-associated modules after AHBVV, in contrast to a response on day 3 after ATIV, which was bracketed by whole blood responses on day 1 as antigen presenting, inflammatory and innate immune cells trafficked to the site of immunization, and on day 5 associated with activated CD4+ T cells. These observations confirm the use of PET/CT, including potentially tissue-, cell-, or cytokine/chemokine-specific radioligands, is a safe and ethical quantitative technique to compare candidate vaccine formulations and could be safely combined with biopsy to guide efficient collection of samples for integrated whole blood and tissue systems vaccinology in small-scale but intensive human clinical models of immunization and to accelerate clinical development and optimisation of vaccine candidates, adjuvants, and formulations., Competing Interests: PD and GG are employees of the GSK group of companies, and report receiving restricted shares of the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Win, Weiner 3rd, Listanco, Patel, Sharma, Greenwood, Maertzdorf, Mollenkopf, Pizzoferro, Cole, Bodinham, Kaufmann, Denoel, Del Giudice and Lewis.)- Published
- 2021
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5. In depth comparative phenotyping of blood innate myeloid leukocytes from healthy humans and macaques using mass cytometry.
- Author
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Elhmouzi-Younes J, Palgen JL, Tchitchek N, Delandre S, Namet I, Bodinham CL, Pizzoferro K, Lewis DJM, Le Grand R, Cosma A, and Beignon AS
- Subjects
- Adult, Animals, Biomarkers metabolism, Cluster Analysis, Female, Flow Cytometry, Humans, Leukocytes metabolism, Macaca, Male, Myeloid Cells metabolism, Phenotype, Immunity, Innate immunology, Leukocytes cytology, Leukocytes immunology, Myeloid Cells cytology, Myeloid Cells immunology
- Abstract
Comparative immune-profiling of innate responses in humans and non-human primates is important to understand the pathogenesis of infectious and chronic inflammatory diseases as well as for the preclinical development of vaccines and immune therapies. However, direct comparisons of the two species are rare and were never performed using mass cytometry. Here, whole-blood-derived leukocytes from healthy humans and cynomolgus macaques were analyzed with mass cytometry. Two similar panels of around 30 monoclonal antibodies targeting human markers associated with innate myeloid cells to stain fixed human and macaque leukocytes were constructed. To compare the circulating innate cells from the two primate species, an analysis pipeline combining a clustering analysis by the Spanning-tree Progression Analysis of Density-normalized Events (SPADE) algorithm with a two-step hierarchical clustering of cells nodes and markers was used. Identical SPADE settings were applied to both datasets, except for the 20 clustering markers which slightly differed. A correlation analysis designed to compare the phenotypes of human and macaque cell nodes and based on 16 markers, including 15 shared clustering markers and CD19 for humans or CD20 for macaques, revealed similarities and differences between staining patterns. This study unique by the number of individuals (26 humans and 5 macaques) and the use of mass cytometry certainly contributes to better assess the advantages and limits of the use of non-human primates in preclinical research. © 2017 International Society for Advancement of Cytometry., (© 2017 International Society for Advancement of Cytometry.)
- Published
- 2017
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6. Regulatory T cell frequencies and phenotypes following anti-viral vaccination.
- Author
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de Wolf ACMT, van Aalst S, Ludwig IS, Bodinham CL, Lewis DJ, van der Zee R, van Eden W, and Broere F
- Subjects
- Adult, Animals, Female, Hepatitis B Vaccines immunology, Hepatitis B Vaccines pharmacology, Humans, Influenza Vaccines immunology, Influenza Vaccines pharmacology, Lymphocyte Count, Male, Mice, Peptide Fragments, Prothrombin, T-Lymphocytes, Regulatory immunology, Vaccines immunology, Vaccines pharmacology, Viral Vaccines immunology, Yellow Fever Vaccine immunology, Yellow Fever Vaccine pharmacology, T-Lymphocytes, Regulatory drug effects, Viral Vaccines pharmacology
- Abstract
Regulatory T cells (Treg) function in the prevention of excessive inflammation and maintenance of immunological homeostasis. However, these cells may also interfere with resolution of infections or with immune reactions following vaccination. Effects of Treg on vaccine responses are nowadays investigated, but the impact of vaccination on Treg homeostasis is still largely unknown. This may be a relevant safety aspect, since loss of tolerance through reduced Treg may trigger autoimmunity. In exploratory clinical trials, healthy adults were vaccinated with an influenza subunit vaccine plus or minus the adjuvant MF59®, an adjuvanted hepatitis B subunit vaccine or a live attenuated yellow fever vaccine. Frequencies and phenotypes of resting (rTreg) and activated (aTreg) subpopulations of circulating CD4+ Treg were determined and compared to placebo immunization. Vaccination with influenza vaccines did not result in significant changes in Treg frequencies and phenotypes. Vaccination with the hepatitis B vaccine led to slightly increased frequencies of both rTreg and aTreg subpopulations and a decrease in expression of functionality marker CD39 on aTreg. The live attenuated vaccine resulted in a decrease in rTreg frequency, and an increase in expression of activation marker CD25 on both subpopulations, possibly indicating a conversion from resting to migratory aTreg due to vaccine virus replication. To study the more local effects of vaccination on Treg in lymphoid organs, we immunized mice and analyzed the CD4+ Treg frequency and phenotype in draining lymph nodes and spleen. Vaccination resulted in a transient local decrease in Treg frequency in lymph nodes, followed by a systemic Treg increase in the spleen. Taken together, we showed that vaccination with vaccines with an already established safe profile have only minimal impact on frequencies and characteristics of Treg over time. These findings may serve as a bench-mark of inter-individual variation of Treg frequencies and phenotypes following vaccination.
- Published
- 2017
- Full Text
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7. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review.
- Author
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Muturi-Kioi V, Lewis D, Launay O, Leroux-Roels G, Anemona A, Loulergue P, Bodinham CL, Aerssens A, Groth N, Saul A, and Podda A
- Subjects
- Databases, Factual, Dysentery, Bacillary prevention & control, Hematologic Tests, Humans, Neutropenia pathology, Randomized Controlled Trials as Topic, Severity of Illness Index, Shigella Vaccines adverse effects, Shigella Vaccines immunology, Shigella sonnei immunology, Neutropenia etiology, Vaccines adverse effects
- Abstract
Background: In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance., Methodology: We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context., Principal Findings: Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations., Conclusions: It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events., Trial Registration: ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287.
- Published
- 2016
- Full Text
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8. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans.
- Author
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Spensieri F, Siena E, Borgogni E, Zedda L, Cantisani R, Chiappini N, Schiavetti F, Rosa D, Castellino F, Montomoli E, Bodinham CL, Lewis DJ, Medini D, Bertholet S, and Del Giudice G
- Subjects
- Adolescent, Adult, Antibodies, Viral blood, Antibodies, Viral immunology, B-Lymphocytes immunology, B-Lymphocytes metabolism, Biomarkers, Hemagglutination Inhibition Tests, Humans, Immunophenotyping, Inducible T-Cell Co-Stimulator Protein metabolism, Influenza A Virus, H1N1 Subtype immunology, Influenza Vaccines immunology, Lymphocyte Activation immunology, Prognosis, Public Health Surveillance, Receptors, CXCR5 metabolism, T-Lymphocyte Subsets metabolism, T-Lymphocytes, Helper-Inducer metabolism, Time Factors, Young Adult, Antibody Formation immunology, Immunity, Lymphocyte Count, T-Lymphocyte Subsets immunology, T-Lymphocytes, Helper-Inducer immunology, Vaccination
- Abstract
CD4+ T follicular helper cells (T(FH)) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4(+)IL-21(+)ICOS1(+) T helper (T(H)) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59(®)-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4(+) T(FH)1 ICOS(+) T(FH) cells and H1N1-specific CD4(+-)IL-21(+)ICOS(+) CXCR5(+) T(FH) and CXCR5(-) T(H) cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4(+) T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these T(FH) cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4(+)T(FH)1 ICOS(+) cells and of H1N1-specific CD4(+)IL-21(+)ICOS(+) CXCR5(+), measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4(+) T(FH) subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity.
- Published
- 2016
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9. Efficacy of increased resistant starch consumption in human type 2 diabetes.
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Bodinham CL, Smith L, Thomas EL, Bell JD, Swann JR, Costabile A, Russell-Jones D, Umpleby AM, and Robertson MD
- Abstract
Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.
- Published
- 2014
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10. Endogenous plasma glucagon-like peptide-1 following acute dietary fibre consumption.
- Author
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Bodinham CL, Al-Mana NM, Smith L, and Robertson MD
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- Adult, Area Under Curve, C-Peptide blood, Cross-Over Studies, Diet, Dietary Supplements, Gastrointestinal Tract metabolism, Gastrointestinal Tract microbiology, Humans, Incretins blood, Insulin blood, Male, Postprandial Period, Resistant Starch, Single-Blind Method, Starch administration & dosage, Young Adult, Dietary Fiber administration & dosage, Glucagon-Like Peptide 1 blood, Starch analogs & derivatives
- Abstract
SCFA resulting from the microbial fermentation of carbohydrates have been linked to increased glucagon-like peptide-1 (GLP-1) secretion from the gastrointestinal tract in cell and animal models; however, there is little direct evidence in human subjects to confirm this. The present study was designed to investigate whether endogenous plasma GLP-1 concentrations increase following acute consumption of 48 g dietary fibre (as resistant starch (RS) from high-amylose maize type 2 RS (HAM-RS2)) compared with a matched placebo. A total of thirty healthy males participated in the present randomised cross-over study where HAM-RS2 or placebo was consumed as part of standardised breakfast and lunch meals. Changes to GLP-1, glucose, insulin and C-peptide were assessed half hourly for 7 h. Following the breakfast meal, plasma GLP-1 concentrations were lower with HAM-RS2 compared with the placebo (P = 0·025). However, there was no significant difference between the supplements following the lunch meal. Plasma insulin concentrations were significantly lower following the lunch meal (P = 0·034) with HAM-RS2 than with the placebo, but were not different after breakfast. Plasma glucose and C-peptide concentrations did not differ at any point. These results suggest that increased dietary fibre intake, in the form of HAM-RS2, does not acutely increase endogenous GLP-1 concentrations in human subjects. Further fibre feeding studies are required to determine whether GLP-1 concentrations may increase following longer-term consumption.
- Published
- 2013
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11. Dietary fibre improves first-phase insulin secretion in overweight individuals.
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Bodinham CL, Smith L, Wright J, Frost GS, and Robertson MD
- Subjects
- Adult, Blood Glucose metabolism, Dietary Supplements, Female, Glucose Tolerance Test, Humans, Insulin Secretion, Male, Overweight blood, Placebos, Dietary Fiber therapeutic use, Insulin metabolism, Overweight drug therapy
- Abstract
Previous work has shown increased insulin sensitivity, increased hepatic insulin clearance and lower postprandial insulin responses following treatment with resistant starch, a type of dietary fibre. The objective of this study was to further explore the effects of resistant starch on insulin secretion. Twelve overweight (BMI 28.2±0.4 kg/m(2)) individuals participated in this randomized, subject-blind crossover study. Participants consumed either 40 g type 2 resistant starch or the energy and carbohydrate-matched placebo daily for four weeks. Assessment of the effect on insulin secretion was made at the end of each intervention using an insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT). Insulin and C-peptide concentrations were significantly higher during the FSIVGTT following the resistant starch compared with the placebo. Modelling of the data showed significantly improved first-phase insulin secretion with resistant starch. These effects were observed without any changes to either body weight or habitual food intake. This study showed that just four weeks of resistant starch intake significantly increased the first-phase insulin secretion in individuals at risk of developing type 2 diabetes. Further studies exploring this effect in individuals with type 2 diabetes are required.
- Published
- 2012
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12. Short-term effects of whole-grain wheat on appetite and food intake in healthy adults: a pilot study.
- Author
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Bodinham CL, Hitchen KL, Youngman PJ, Frost GS, and Robertson MD
- Subjects
- Adult, Body Weight drug effects, Bread, Cross-Over Studies, Diet Records, Dietary Carbohydrates pharmacology, Female, Food Handling, Humans, Male, Pilot Projects, Reference Values, Satiation drug effects, Appetite drug effects, Blood Pressure drug effects, Dietary Carbohydrates administration & dosage, Edible Grain, Energy Intake drug effects, Triticum
- Abstract
While it has been proposed, based on epidemiological studies, that whole grains may be beneficial in weight regulation, possibly due to effects on satiety, there is limited direct interventional evidence confirming this. The present cross-over study aimed to investigate the short-term effects on appetite and food intake of 48 g of whole-grain wheat (daily for 3 weeks) compared with refined grain (control). A total of fourteen healthy normal-weight adults consumed, within their habitual diets, either two whole-grain bread rolls (providing 48 g of whole grains over two rolls) or two control rolls daily for 3 weeks. Changes in food intake were assessed using 7 d diet diaries. Changes in subjective appetite ratings and food intake were also assessed at postprandial study visits. There were no significant differences between interventions in energy intake (assessed by the 7 d diet diaries and at the ad libitum test meal), subjective appetite ratings or anthropometric measurements. However, there was a significant difference between interventions for systolic blood pressure, which decreased during the whole-grain intervention and increased during the control intervention (-2 v. 4 mmHg; P = 0·015). The present study found no effect of whole grains on appetite or food intake in healthy individuals; however, 48 g of whole grain consumed daily for 3 weeks did have a beneficial effect on systolic blood pressure. The findings from the present study therefore do not support epidemiological evidence that whole grains are beneficial in weight regulation, although further investigation in other population groups (such as overweight and obese) would be required.
- Published
- 2011
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