Immune mechanisms of vaccine induced protection against chronic hepatitis C virus infection in chimpanzees

Hepatitis C virus (HCV) infection is characterized by a high propensity for development of life-long viral persistence. An estimated 170 million people suffer from chronic hepatitis caused by HCV. Currently, there is no approved prophylactic HCV vaccine available. With the near disappearance of the most relevant animal model for HCV, the chimpanzee, we review the progression that has been made regarding prophylactic vaccine development against HCV. We describe the results of the individual vaccine evaluation experiments in chimpanzees, in relation to what has been observed in humans. The results of the different studies indicate that partial protection against infection can be achieved, but a clear correlate of protection has thus far not yet been defined.</p

Checkpoint Inhibitors and Therapeutic Vaccines for the Treatment of Chronic HBV Infection

Treatment of chronic hepatitis B virus (HBV) infection is highly effective in suppressing viral replication, but complete cure is rarely achieved. In recent years, substantial progress has been made in the development of immunotherapy to treat cancer. Applying these therapies to improve the management of chronic HBV infection is now being attempted, and has become an area of active research. Immunotherapy with vaccines and checkpoint inhibitors can boost T cell functions in vitro, and therefore may be used to reinvigorate the impaired HBV-specific T cell response. However, whether these approaches will suffice and restore antiviral T cell immunity to induce long-term HBV control remains an open question. Recent efforts have begun to describe the phenotype and function of HBV-specific T cells on the single epitope level. An improved understanding of differing T cell specificities and their contribution to HBV control will be instrumental for advancement of the field. In this review, we outline correlates of successful versus inadequate T cell responses to HBV, and discuss the rationale behind therapeutic vaccines and checkpoint inhibitors for the treatment of chronic HBV infection

DNA methylation markers in the detection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and has a poor prognosis. Epigenetic modification has been shown to be deregulated during HCC development by dramatically impacting the differentiation, proliferation, and function of cells. One important epigenetic modification is DNA methylation during which methyl groups are added to cytosines without changing the DNA sequence itself. Studies found that methylated DNA markers can be specific for detection of HCC. On the basis of these findings, the utility of methylated DNA markers as novel biomarkers for early-stage HCC has been measured in blood, and indeed superior sensitivity and specificity have been found in several studies when compared to current surveillance methods. However, a variety of factors currently limit the immediate application of these exciting biomarkers. In this review, we provide a detailed rationalisation of the approach and basis for the use of methylation biomarkers for HCC detection and summarise recent studies on methylated DNA markers in HCC focusing on the importance of the aetiological cause of liver disease in the mechanisms leading to cancer.</p

Immune mechanisms of vaccine induced protection against chronic hepatitis C virus infection in chimpanzees

Hepatitis C virus (HCV) infection is characterized by a high propensity for development of life-long viral persistence. An estimated 170 million people suffer from chronic hepatitis caused by HCV. Currently, there is no approved prophylactic HCV vaccine available. With the near disappearance of the most relevant animal model for HCV, the chimpanzee, we review the progression that has been made regarding prophylactic vaccine development against HCV. We describe the results of the individual vaccine evaluation experiments in chimpanzees, in relation to what has been observed in humans. The results of the different studies indicate that partial protection against infection can be achieved, but a clear correlate of protection has thus far not yet been defined

Implementation of LOFAR RFI mitigation strategy

ASTRON is building the world’s largest radio telescope for low frequencies, LOFAR. LOFAR is optimized for detecting astronomical signals in the 30-80 MHz and 120-240 MHz frequency windows. Since this part of the spectrum is in extensive use by others, a special RFI mitigation strategy is implemented which will be described in the paper. International RFI measurements will be presented and we will focus on practical implementation issues such as the impact of Digital Video Broadcast, RF emissions from power lines and the influence of large wind turbines on the EM environmen

Validation of whole blood rapid diagnosis test for hepatitis b

We recently published a report validating point-of-care rapid diagnostic tests (RDT) for the diagnosis of Hepatitis B virus (HBV) infection in serum. In the current report, we validated a whole-blood RDT for HBsAg in the form of a test-strip. The test was validated in 55 HBV positive individuals across all geno-types other than F, and in 20 HBV negative individuals in the Netherlands. The RDT showed 100% sensi-tivity and specificity. The low cost and use in whole blood allows this RDT to be useful in resource-limited locations, further validation in such settings will be of importance

Understanding IFNλ in rheumatoid arthritis

Unraveling the mechanisms underlying the inflammatory response in rheumatoid arthritis is crucial in order to better understand the disease and to develop novel therapeutic approaches. Although the effect of type I interferons on fibroblasts and in the context of rheumatoid arthritis has been described for some time, little is known on the effects of the type III interferons, also known as IFNλ. In a previous issue, Xu and colleagues demonstrate that one of the members of the IFNλ family, IFNλ1, enhances Toll-like receptor expression and consequently promotes the production of proinflammatory cytokines known to be involved in initiating and maintaining the inflammatory responses in rheumatoid arthritis

Association between a progesterone receptor mutation and hepatitis E sero-positivity in liver transplant recipients

Problem: We investigated if the PROGINS mutation increases the risk of hepatitis E virus (HEV) infection in liver transplant recipients. PROGINS was analyzed through KASP assay; HEV serologies assessed via enzyme-linked immunosorbent assay and multiplex cytokine assays were evaluated in plasma with the ProcartaPlex human immunoassay. Seventy liver transplant recipients were evaluated, of which 23 (33%) were HEV immunoglobuln G (IgG)-positive (HEV+). The frequency of PROGINS in the HEV+ group was 34%, compared with 14% in those that were HEV IgG negative (HEV−). Cytokine measurements in a sub-set of samples from HEV+/PROGINS+ individuals showed decreased plasma levels of monokine induced by gamma interferon, a proliferation-inducing ligand, and stem cell factor, as well as increased levels of eotaxin-3 and interleukin-31 compared with those HEV−/PROGINS− samples. Our findings suggest an association between the PROGINS mutation and seropositivity for HEV in liver transplant recipients with consequent distorted cytokine levels