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. 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.

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. 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.

A hypnotherapy intervention for the treatment of anxiety in patients with cancer receiving palliative care.

This pilot study aimed to assess the benefits of hypnotherapy in the management of anxiety and other symptoms, including depression and sleep disturbance, in palliative care patients with cancer. Eleven hospice patients received four sessions of hypnotherapy and completed the Hospital Anxiety and Depression Scale, the Edmonton Symptom Assessment System, and the Verran and Snyder-Halpern Scale at set time points. Wrist actigraphy also provided an objective assessment of sleep quality. After the second hypnotherapy session there was a statistically significant reduction in mean anxiety and symptom severity, but not in depression or sleep disturbance. After the fourth session there was a statistically significant reduction in all four patient-reported measures but not in actigraphy. These results offer evidence that hypnotherapy can reduce anxiety in palliative care patients, as well as improving sleep and the severity of psychological and physical symptoms. Further studies are needed to explore whether the observed benefits were a direct result of the hypnotherapy and how the intervention could most benefit this patient population.

Sleep duration and quality in elite athletes measured using wristwatch actigraphy.

Sleep is known to be an important component of recovery from training, yet little is known about the quality and quantity of sleep achieved by elite athletes. The aim of the present study was to quantify sleep in elite athletes using wristwatch actigraphy. Individual nights of sleep from a cohort of Olympic athletes (n = 47) from various sports were analysed and compared to non-athletic controls (n = 20). There were significant differences between athletes and controls in all measures apart from 'time asleep' (p = 0.27), suggesting poorer characteristics of sleep in the athlete group. There was a significant effect of gender on 'time awake' (mean difference: 12 minutes higher in males; 95% likely range: 3 to 21 minutes) and 'sleep efficiency' (mean difference: 2.4 lower in males; 95% likely range: 0.1 to 4.8). Athletes showed poorer markers of sleep quality than an age and sex matched non-athletic control group (Sleep efficiency: 80.6 ± 6.4% and 88.7 ± 3.6%, respectively. Fragmentation Index: 36.0 ± 12.4 and 29.8 ± 9.0, respectively) but remained within the range for healthy sleep. This descriptive study provides novel data for the purpose of characterising sleep in elite athletes.