Ebola virus glycoprotein stimulates IL-18 dependent natural killer cell responses

BACKGROUNDNK cells are activated by innate cytokines and viral ligands to kill virus-infected cells. These functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined.METHODSThe novel 2-dose heterologous Adenovirus type 26.ZEBOV (Ad26.ZEBOV) and modified vaccinia Ankara-BN-Filo (MVA-BN-Filo) vaccine regimen is safe and provides specific immunity against Ebola glycoprotein, and is currently in phase 2 and 3 studies. Here, we analyzed NK cell phenotype and function in response to Ad26.ZEBOV, MVA-BN-Filo vaccination regimen and in response to in vitro Ebola glycoprotein stimulation of PBMCs isolated before and after vaccination.RESULTSWe show enhanced NK cell proliferation and activation after vaccination compared with baseline. Ebola glycoprotein-induced activation of NK cells was dependent on accessory cells and TLR-4-dependent innate cytokine secretion (predominantly from CD14+ monocytes) and enriched within less differentiated NK cell subsets. Optimal NK cell responses were dependent on IL-18 and IL-12, whereas IFN-γ secretion was restricted by high concentrations of IL-10.CONCLUSIONThis study demonstrates the induction of NK cell effector functions early after Ad26.ZEBOV, MVA-BN-Filo vaccination and provides a mechanism for the activation and regulation of NK cells by Ebola glycoprotein.TRIAL REGISTRATIONClinicalTrials.gov NCT02313077.FUNDINGUnited Kingdom Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (grant 115861) and Crucell Holland (now Janssen Vaccines and Prevention B.V.), European Union's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA)

Antibody-Dependent Natural Killer Cell Activation after Ebola Vaccination

BACKGROUND:Antibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein antibodies suggest that Fc-dependent activation of effector cells, including NK cells, could play a role in vaccination against Ebola virus disease. METHODS:We analysed the effect of anti-Ebola glycoprotein antibody in the serum of U.K.-based volunteers vaccinated with the novel 2-dose heterologous Adenovirus type 26.ZEBOV, Modified Vaccinia Ankara-BN-Filo vaccine regimen, on primary human NK cell activation. RESULTS:We demonstrate primary human NK cell CD107a and IFN-γ expression, combined with downregulation of CD16, in response to recombinant Ebola virus glycoprotein and post-vaccine dose 1 and dose 2 sera. These responses varied significantly with vaccine regimen and NK cell activation was found to correlate with anti-glycoprotein antibody concentration. We also reveal an impact of NK cell differentiation phenotype on antibody-dependent NK cell activation, with highly differentiated CD56dimCD57+ NK cells being the most responsive. CONCLUSIONS:This study thus highlights the dual importance of vaccine-induced antibody concentration and NK cell differentiation status in promoting Fc-mediated activation of NK cells after vaccination, raising a potential role for antibody-mediated NK cell activation in vaccine-induced immune responses

The Effect of Moist Hot Packs on Tissue Extensibility

Moist heat represents a modality that employs superficial thermal energy to treat a diverse range of impairments of the musculoskeletal and neuromuscular systems. One particular impairment that can be treated by the application of moist heat is tissue extensibility. Moist heat influences tissue extensibility by altering viscoelastic properties of tissue such as decreasing fluid viscosity, relaxing cross-links of collagen fibers, and decreasing joint and muscle stiffness. This project seeks to review the current research on the impact of moist heat on tissue extensibility

Clinical benefits, referral practice and cost implications of an in-hospital pain service: results of a service evaluation in a London teaching hospital.

BACKGROUND In-hospital pain services (IPS) are commonplace, but evidence of efficacy is inadequate, and patients' pain management in any hospital ward remains problematic. This service evaluation aimed to measure the effect of a contemporary IPS, its appropriate use and cost-efficacy. METHODS Records of 249 adults reviewed by the IPS in an inner London Teaching Hospital over an 8-month period were analysed for demographic data, interventions, workload and change in pain intensity measured by numerical rating scale (NRS). Non-parametric tests were used to evaluate differences between initial and final NRS. Spearman's rank correlation analysis was used to create a correlation matrix to evaluate associations between all identified independent variables with the change in NRS. All strongly correlated variables (ρ > 0.5) were subsequently included in a binary logistic regression analysis to identify predictors of pain resolution greater than 50% NRS and improvement rather than deterioration or no change in NRS. Finally, referral practice and cost of inappropriate referrals were estimated. Referrals were thought to be inappropriate when pain was not optimised by the referring team; they were identified using a set algorithm. RESULTS Initial median NRS and final median NRS were significantly different when a Wilcoxon signed-rank test was applied to the whole cohort; Z = -5.5 (p = 0.000). Subgroup analysis demonstrated no significant difference in the 'mild' pain group; z = -1.1 (p = 0.253). Regression analysis showed that for every unit increase in initial NRS, there was a 62% chance of general and a 33% chance of >50% improvement in final NRS. An estimated annual cost-saving potential of £1546 to £4558 was found in inappropriate referrals and patients experiencing no benefit from the service. DISCUSSION Results suggest that patients with moderate to severe pain benefit most from IPS input. Also pain management resources are often distributed inefficiently. Future research is required to develop algorithms for easy identification of potential treatment responders

Afri-Can Forum 2

CITATION: Mukudu, H., et al. 2016. Afri-Can Forum 2. BMC Infectious Diseases, 16:315, doi:10.1186/s12879-016-1466-6.The original publication is available at https://bmcinfectdis.biomedcentral.comENGLISH ABSTRACT: We are pleased to present peer reviewed forum proceedings of the 2nd synchronicity forum of GHRI/CHVIfunded Canadian and African HIV prevention and vaccine teams Forum objectives ∙GHRI-funded capacity building and HIV prevention research teams presented highlights of achievements ∙Teams discussed how to jointly build on achievements for sustainability ∙Provided an opportunity for inter-team collaboration, synchronize best approach to capacity building, mentoring of new researchers and building leadership ∙Provided opportunities for informal discussions and networking among the teams. ∙Teams learnt about recent advances in the area of African regulatory and ethics review process ∙The forum proceedings was a special supplement in an openaccess journal was producedhttps://bmcinfectdis.biomedcentral.com/articles/supplements/volume-16-supplement-2Publisher's versio