Cynomolgus macaques as a translational model of human immune responses to yellow fever 17D vaccination.

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.

Systematic Evaluation of Kinetics and Distribution of Muscle and Lymph Node Activation Measured by F-FDG- and C-PBR28-PET/CT Imaging, and Whole Blood and Muscle Transcriptomics After Immunization of Healthy Humans With Adjuvanted and Unadjuvanted Vaccines.

Systems vaccinology has been applied to detect signatures of human vaccine induced immunity but its ability, together with high definition 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).

Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium.

Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies.

Regulatory T cell frequencies and phenotypes following anti-viral vaccination.

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.

In depth comparative phenotyping of blood innate myeloid leukocytes from healthy humans and macaques using mass cytometry.

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.

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review.

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.

Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans.

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.

Endogenous plasma glucagon-like peptide-1 following acute dietary fibre consumption.

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.

Dietary fibre improves first-phase insulin secretion in overweight individuals.

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.

Short-term effects of whole-grain wheat on appetite and food intake in healthy adults: a pilot study.

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.

Acute ingestion of resistant starch reduces food intake in healthy adults.

Resistant starch (RS), a non-viscous dietary fibre, may have postprandial effects on appetite regulation and metabolism, although the exact effects and mechanisms are unknown. An acute randomised, single-blind crossover study, aimed to determine the effects of consumption of 48 g RS on appetite compared to energy and available carbohydrate-matched placebo. Twenty young healthy adult males consumed either 48 g RS or the placebo divided equally between two mixed meals on two separate occasions.