Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage

AbstractBackground4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. Assessment of 4CMenB strain coverage in specific epidemiologic settings is of primary importance to predict vaccination impact on the burden of disease. The Meningococcal Antigen Typing System (MATS) was developed to predict 4CMenB strain coverage, using serum bactericidal antibody assay with human complement (hSBA) data from a diverse panel of strains not representative of any specific epidemiology.ObjectiveTo experimentally validate the accuracy of MATS-based predictions against strains representative of a specific epidemiologic setting.Methods and resultsWe used a stratified sampling method to identify a representative sample from all MenB disease isolates collected from England and Wales in 2007–2008, tested the strains in the hSBA assay with pooled sera from infant and adolescent vaccinees, and compared these results with MATS. MATS predictions and hSBA results were significantly associated (P=0.022). MATS predicted coverage of 70% (95% CI, 55–85%) was largely confirmed by 88% killing in the hSBA (95% CI, 72–95%). MATS had 78% accuracy and 96% positive predictive value against hSBA.ConclusionMATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents

High Data Output and Automated 3D Correlative Light–Electron Microscopy Method

Correlative light/electron microscopy (CLEM) allows the simultaneous observation of a given subcellular structure by fluorescence light microscopy (FLM) and electron microscopy. The use of this approach is becoming increasingly frequent in cell biology. In this study, we report on a new high data output CLEM method based on the use of cryosections. We successfully applied the method to analyze the structure of rough and smooth Russell bodies used as model systems. The major advantages of our method are (i) the possibility to correlate several hundreds of events at the same time, (ii) the possibility to perform three-dimensional (3D) correlation, (iii) the possibility to immunolabel both endogenous and recombinantly expressed proteins at the same time and (iv) the possibility to combine the high data analysis capability of FLM with the high precision–accuracy of transmission electron microscopy in a CLEM hybrid morphometry analysis. We have identified and optimized critical steps in sample preparation, defined routines for sample analysis and retracing of regions of interest, developed software for semi/fully automatic 3D reconstruction and defined preliminary conditions for an hybrid light/electron microscopy morphometry approach

Design of Thermal Exchange, a microgravity experiment on-board the International Space Station

The International Space Station was mainly thought as an orbiting research laboratory and, as such, it comprises several resources to test and validate new technologies to be used in future space missions. This paper presents the design and development of Thermal Exchange, a microgravity experiment that aims at on-orbit validation of low-toxicity heat pipe performance for thermal control of future spacecraft, both manned and unmanned. Tendency for future space systems points towards simplicity, limited maintenance needs and high reliability. In particular, vehicle thermal control should be based on passive systems, requiring low maintenance and very limited remote control. Accordingly, heat-pipes are good candidates for future spacecraft thermal control, due to their low complexity and maintenance requirement, as well as their high reliability. In this scenario, Thermal Exchange aims at the development of a payload for the demonstration, in microgravity conditions, of heat pipes and low toxicity working fluids, which would make it compatible with human applications (habitable modules) as well. Thermal Exchange is a sub-rack payload that will be operated inside the Microgravity Science Glovebox (MSG) on-board the International Space Station (ISS). Thermal Exchange consists of a main housing that accommodates the experiment and the avionics containers: the experiment container includes four axially grooved heat pipes filled with low-toxicity working fluids and mixtures, whereas the avionics container encloses three electronic boards to perform power management and distribution, health management and on-board data handling autonomously once on-board the ISS. Thermal Exchange will be launched with the Space-X 9 launch vehicle inside a half CTB (Cargo Transfer Bag). Thermal Exchange will be uninstalled and stowed at the end of the on-orbit operations and will re-enter with the Space-X 10 vehicle. This paper first provides a general overview of Thermal Exchange and the project schedule, including the operations to be carried out on the ISS. Then, it deals with the design and development of the ground and flight models. Main results are presented and discussed. Eventually main conclusions are drawn

THERMAL EXCHANGE: A PAYLOAD FOR TECHNOLOGICAL EXPERIMENTS ON-BOARD THE INTERNATIONAL SPACE STATION

The International Space Station was mainly thought as an orbiting research laboratory and, as such, it comprises several resources to test and validate new technologies to be used in future space missions. This paper presents the progresses in the design and development process of Thermal Exchange, an experiment that aims at on-orbit validation of low-toxicity heat pipe performance for thermal control of future spacecraft, both manned and unmanned. Tendency for future space systems points towards simplicity, limited maintenance needs and high reliability. In particular, thermal control should be based on passive systems, requiring low maintenance and very limited remote control. Accordingly, heat-pipes are good candidates for future spacecraft thermal control, due to their low complexity and maintenance need, as well as their high reliability. In this scenario, Thermal Exchange aims at the development of a payload for the demonstration, in microgravity conditions, of heat pipes and low toxicity working fluids, which would make it compatible with human applications (habitable modules) as well. Thermal Exchange is a sub-rack payload that will be operated inside the Microgravity Science Glovebox (MSG) on-board the International Space Station (ISS). Thermal Exchange consists of a main housing that accommodates the experiment and the avionics containers: the experiment container includes four axially grooved heat pipes filled with low-toxicity working fluids and mixtures, whereas the avionics container encloses three electronic boards to perform power management and distribution, health management and on-board data handling autonomously once on-board the ISS. Thermal Exchange will be launched with SpaceX-9 launch vehicle in 2016 inside an half CTB (Cargo Transfer Bag). Thermal Exchange will be uninstalled and stowed at the end of the on-orbit operations and will re-entry on Earth with SpaceX-10 launch vehicle. This paper first provides a general overview of Thermal Exchange and the project schedule, including the operations to be carried out on the ISS. Then, it deals with the development of the ground and flight models, highlighting first the differences between the models and then focusing on the assembly integration and test of both models. Main results are presented and discussed. Eventually main conclusions are draw

Design of Thermal Exchange, a microgravity experiment on-board the International Space Station

The International Space Station was mainly thought as an orbiting research laboratory and, as such, it comprises several resources to test and validate new technologies to be used in future space missions. This paper presents the design and development of Thermal Exchange, a microgravity experiment that aims at on-orbit validation of low-toxicity heat pipe performance for thermal control of future spacecraft, both manned and unmanned. Tendency for future space systems points towards simplicity, limited maintenance needs and high reliability. In particular, vehicle thermal control should be based on passive systems, requiring low maintenance and very limited remote control. Accordingly, heat-pipes are good candidates for future spacecraft thermal control, due to their low complexity and maintenance requirement, as well as their high reliability. In this scenario, Thermal Exchange aims at the development of a payload for the demonstration, in microgravity conditions, of heat pipes and low toxicity working fluids, which would make it compatible with human applications (habitable modules) as well. Thermal Exchange is a sub-rack payload that will be operated inside the Microgravity Science Glovebox (MSG) on-board the International Space Station (ISS). Thermal Exchange consists of a main housing that accommodates the experiment and the avionics containers: the experiment container includes four axially grooved heat pipes filled with low-toxicity working fluids and mixtures, whereas the avionics container encloses three electronic boards to perform power management and distribution, health management and on-board data handling autonomously once on-board the ISS. Thermal Exchange will be launched with the Space-X 9 launch vehicle inside a half CTB (Cargo Transfer Bag). Thermal Exchange will be uninstalled and stowed at the end of the on-orbit operations and will re-enter with the Space-X 10 vehicle. This paper first provides a general overview of Thermal Exchange and the project schedule, including the operations to be carried out on the ISS. Then, it deals with the design and development of the ground and flight models. Main results are presented and discussed. Eventually main conclusions are drawn

THERMAL EXCHANGE: A PAYLOAD FOR TECHNOLOGICAL EXPERIMENTS ON-BOARD THE INTERNATIONAL SPACE STATION

The International Space Station was mainly thought as an orbiting research laboratory and, as such, it comprises several resources to test and validate new technologies to be used in future space missions. This paper presents the progresses in the design and development process of Thermal Exchange, an experiment that aims at on-orbit validation of low-toxicity heat pipe performance for thermal control of future spacecraft, both manned and unmanned. Tendency for future space systems points towards simplicity, limited maintenance needs and high reliability. In particular, thermal control should be based on passive systems, requiring low maintenance and very limited remote control. Accordingly, heat-pipes are good candidates for future spacecraft thermal control, due to their low complexity and maintenance need, as well as their high reliability. In this scenario, Thermal Exchange aims at the development of a payload for the demonstration, in microgravity conditions, of heat pipes and low toxicity working fluids, which would make it compatible with human applications (habitable modules) as well. Thermal Exchange is a sub-rack payload that will be operated inside the Microgravity Science Glovebox (MSG) on-board the International Space Station (ISS). Thermal Exchange consists of a main housing that accommodates the experiment and the avionics containers: the experiment container includes four axially grooved heat pipes filled with low-toxicity working fluids and mixtures, whereas the avionics container encloses three electronic boards to perform power management and distribution, health management and on-board data handling autonomously once on-board the ISS. Thermal Exchange will be launched with SpaceX-9 launch vehicle in 2016 inside an half CTB (Cargo Transfer Bag). Thermal Exchange will be uninstalled and stowed at the end of the on-orbit operations and will re-entry on Earth with SpaceX-10 launch vehicle. This paper first provides a general overview of Thermal Exchange and the project schedule, including the operations to be carried out on the ISS. Then, it deals with the development of the ground and flight models, highlighting first the differences between the models and then focusing on the assembly integration and test of both models. Main results are presented and discussed. Eventually main conclusions are drawn

Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment.

International audienceBACKGROUND:A novel multicomponent vaccine against meningococcal capsular group B (MenB) disease contains four major components: factor-H-binding protein, neisserial heparin binding antigen, neisserial adhesin A, and outer-membrane vesicles derived from the strain NZ98/254. Because the public health effect of the vaccine, 4CMenB (Novartis Vaccines and Diagnostics, Siena, Italy), is unclear, we assessed the predicted strain coverage in Europe.METHODS:We assessed invasive MenB strains isolated mainly in the most recent full epidemiological year in England and Wales, France, Germany, Italy, and Norway. Meningococcal antigen typing system (MATS) results were linked to multilocus sequence typing and antigen sequence data. To investigate whether generalisation of coverage applied to the rest of Europe, we also assessed isolates from the Czech Republic and Spain.FINDINGS:1052 strains collected from July, 2007, to June, 2008, were assessed from England and Wales, France, Germany, Italy, and Norway. All MenB strains contained at least one gene encoding a major antigen in the vaccine. MATS predicted that 78% of all MenB strains would be killed by postvaccination sera (95% CI 63-90, range of point estimates 73-87% in individual country panels). Half of all strains and 64% of covered strains could be targeted by bactericidal antibodies against more than one vaccine antigen. Results for the 108 isolates from the Czech Republic and 300 from Spain were consistent with those for the other countries.INTERPRETATION:MATS analysis showed that a multicomponent vaccine could protect against a substantial proportion of invasive MenB strains isolated in Europe. Monitoring of antigen expression, however, will be needed in the future