Differential effects of glycoprotein B epitope-specific antibodies on human cytomegalovirus-induced cell–cell fusion

Attachment of, and cell–cell fusion induced by, human cytomegalovirus were studied in the presence of neutralizing monospecific antibodies against antigenic domains 1 (AD-1) or 2 (AD-2) of glycoprotein B (gB, gpUL55). Efficient inhibition of the virion-mediated fusion event was consistently observed for the human AD-2-specific antibody as determined by a reporter gene activation assay based on permissive astrocytoma cells. In contrast, antibodies directed against the major neutralizing gB epitope AD-1 reduced fusion only by 20–60 %. Virus attachment via heparan sulfate was unaffected by the antibodies under the conditions used. Virus receptor binding as examined by heparin treatment of adsorbed virus was significantly reduced only if the virus had been coated with the AD-2-specific antibody. Neutralization of virus infectivity by the AD-2-specific antibody thus seems most likely to result from interference with a receptor-binding event during initial virus–host cell interaction

Rituximab Mediates a Strong Elevation of B-Cell-Activating Factor Associated with Increased Pathogen-Specific IgG but Not Autoantibodies in Pemphigus Vulgaris

Pemphigus vulgaris (PV) is a severe autoimmune disease affecting the skin and mucous membranes, characterized by autoantibodies mainly against desmoglein 3 (dsg3). This study investigated the effects of different treatment options on two B-cell mediators, B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), in 19 PV patients on immunosuppressive drugs alone or in combination with immunoadsorption and anti-CD20 antibody, respectively. Serum BAFF and APRIL levels, circulating desmoglein-reactive autoantibodies, and serum IgG specific for varicella-zoster virus (VZV) and Epstein–Barr virus (EBV) were determined by ELISA before and at different time points after initiation of the respective therapy. In contrast to immunosuppressive therapy alone and in combination with adjuvant immunoadsorption, respectively, rituximab treatment led to a strong and significant elevation of BAFF, but not of APRIL levels, which normalized upon recovery of peripheral CD19+ B cells. Moreover, rituximab treatment led to a statistically significant increase of anti-VZV-IgG and anti-EBV-IgG titers, whereas anti-dsg1 and -3 specific autoantibody titers decreased significantly. Our results suggest that elevated BAFF levels might exert a differential effect on the induction of autoreactive versus pathogen-specific IgG antibody production in PV patients, possibly due to promotion of antibody release of pathogen-specific long-lived plasma cells

Blood Screening for Influenza

Influenza viruses, including highly pathogenic avian influenza virus (H5N1), could threaten blood safety. We analyzed 10,272 blood donor samples with a minipool nucleic acid amplication technique. Analytical sensitivity of the method was 804 geq/mL and 444 geq/mL for generic influenza primers and influenza (H5N1) subtype–specific primers. This study demonstrates that such screening for influenza viruses is feasible

Huddle Up: Using Mediation to Help Settle the National Football League Labor Dispute

In a patient transferred from Togo to Cologne, Germany, Lassa fever was diagnosed 12 days post mortem. Sixty-two contacts in Cologne were categorised according to the level of exposure, and gradual infection control measures were applied. No clinical signs of Lassa virus infection or Lassa specific antibodies were observed in the 62 contacts. Thirty-three individuals had direct contact to blood, other body fluids or tissue of the patients. Notably, with standard precautions, no transmission occurred between the index patient and healthcare workers. However, one secondary infection occurred in an undertaker exposed to the corpse in Rhineland-Palatinate, who was treated on the isolation unit at the University Hospital of Frankfurt. After German authorities raised an alert regarding the imported Lassa fever case, an American healthcare worker who had cared for the index patient in Togo, and who presented with diarrhoea, vomiting and fever, was placed in isolation and medevacked to the United States. The event and the transmission of Lassa virus infection outside of Africa underlines the need for early diagnosis and use of adequate personal protection equipment (PPE), when highly contagious infections cannot be excluded. It also demonstrates that larger outbreaks can be prevented by infection control measures, including standard PPE

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.)

Innovative Sicherungstechnik mit optischen Systemen

Optische Sensoren werden im Schienenverkehr bislang für Anwendungen ohne oder mit nur geringer Sicherheitsrelevanz verwendet. Der Artikel beschreibt Anwendungsbereiche für den möglichen Einsatz optischer Sensoren im Schienenverkehr für höhere Sicherheitsrelevanz. Anhand eines Demonstrators, der die Einsatzfähigkeit optischer Systeme für unterschiedliche Funktionen an Bahnübergängen aufzeigen soll, werden die Aspekte Sicherheit, Verfügbarkeit, Zuverlässigkeit, betriebliches Umfeld und Kostenstrukturen beschrieben. Dabei wird die Frage der zunehmenden Sicherheitsrelevanz von der Funktion „Anrufen“ bis „Gefahrenraumfreimeldung“ thematisiert. Das Thema „Bahnübergang“ bietet auch einen Anwendungsbereich für Innovationen auf Basis kostengünstiger Technologien, die möglicherweise zu einem effizienteren Betrieb der Schieneninfrastruktur beitragen können

Endocytosis of the Nipah Virus Glycoproteins

Nipah virus (NiV), a highly pathogenic member of the family Paramyxoviridae, encodes the surface glycoproteins F and G. Since internalization of the NiV envelope proteins from the cell surface might be of functional importance for viral pathogenesis either by regulating cytopathogenicity or by modulating recognition of infected cells by the immune system, we analyzed the endocytosis of the NiV F and G proteins. Interestingly, we found both glycoproteins to be internalized in infected and transfected cells. As endocytosis is normally mediated by tyrosine- or dileucine-dependent signals in the cytoplasmic tails of transmembrane proteins, all potential internalization signals in the NiV glycoproteins were mutated. Whereas the G protein appeared to be constitutively internalized with the bulk flow during membrane turnover, uptake of the F protein was found to be signal mediated. F endocytosis clearly depended on a membrane-proximal YXXΦ motif and was found to be of functional importance for the biological activity of the protein

Generic Operational Requirements for Video based Applications at Level Crossings

The implementation of video based technology can help to increase the safety at level crossings. To implement and admit an innovative video based supervision system at level crossings intensive test campaigns are necessary, the generic operational requirements have to be identified and a lot of discussions with assessors can help to find the suitable solution. Technical and operational solutions for level crossings are analyzed concerning safety, economy, availability and operation. One possibility are video based technologies for safety relevant applications at level crossing. Worldwide a lot of level crossings without any obstacle detection in different structural and operational constellations exist momentarily. Therefore the Institute of Transportation Systems of the DLR investigates the options for technical realized vacancy detection for the danger zone of level crossings and an automatically activation of the level crossing system. None of the existing video based technologies, which are in work at railway system, are safety relevant applications (in Germany). They only assist the operators of the German railways, like an application based on video for monitoring level crossing through signaler. The video based level crossing monitoring is only used as a technical aided system for the signal man to observe a distant level crossing. The protection of the level crossing against unauthorized crossing is still not realized by using video. The presentation will show a video based system to improve safety at level crossing across Europe. Furthermore, the specific operational rules for a video based supervision system will be sketched. Generic operational requirements are identified. A lot of ideas, how video based technology can improve safety at level crossing are described. The range of ideas includes technical and non-technical secured level crossings. Innovative systems using camera based technology can be an economical alternative to existing units. The Institute of Transportation Systems of the German Aerospace Center in Braunschweig is developing such a system and evaluates it in different field tests