Exospheric Temperature Measured by NASA-GOLD Under Low Solar Activity: Comparison With Other Data Sets.

Exospheric temperature is one of the key parameters in constructing thermospheric models and has been extensively studied with in situ observations and remote sensing. The Global-scale Observations of the Limb and Disk (GOLD) at a geosynchronous vantage point provides dayglow limb images for two longitude sectors, from which we can estimate the terrestrial exospheric temperature since 2018. In this paper, we investigate climatological behavior of the exospheric temperature measured by GOLD.

High dissolved oxygen tension triggers outer membrane vesicle formation by Neisseria meningitidis.

Background: Outer membrane vesicles (OMVs) are nanoparticles released by Gram-negative bacteria and can be used as vaccines. Often, detergents are used to promote release of OMVs and to remove the toxic lipopolysaccharides. Lipopolysaccharides can be detoxified by genetic modification such that vesicles spontaneously produced by bacteria can be directly used as vaccines.

Global Ionospheric and Thermospheric Effects of the June 2015 Geomagnetic Disturbances: Multi-Instrumental Observations and Modeling.

By using data from multiple instruments, we investigate ionospheric/thermospheric behavior during the period from 21 to 23 June 2015, when three interplanetary shocks (IS) of different intensities arrived at Earth. The first IS was registered at 16:45 UT on 21 June and caused ~50 nT increase in the SYM-H index. The second IS arrived at 5:45 UT on 22 June and induced an enhancement of the auroral/substorm activity that led to rapid increase of thermospheric neutral mass density and ionospheric vertical total electron content at high latitudes.

Proteome Analysis Is a Valuable Tool to Monitor Antigen Expression during Upstream Processing of Whole-Cell Pertussis Vaccines.

Physicochemical and immunochemical assays were applied to substantiate the relation between upstream processing and the quality of whole-cell pertussis vaccines. Bordetella pertussis bacteria were cultured on a chemically defined medium using a continuous cultivation process in stirred tank reactors to obtain uniform protein expression. Continuous culture favors the consistent production of proteins known as virulence factors.

HPAEC-PAD quantification of Haemophilus influenzae type b polysaccharide in upstream and downstream samples.

Due to the rapidly increasing introduction of Haemophilus influenzae type b (Hib) and other conjugate vaccines worldwide during the last decade, reliable and robust analytical methods are needed for the quantitative monitoring of intermediate samples generated during fermentation (upstream processing, USP) and purification (downstream processing, DSP) of polysaccharide vaccine components. This study describes the quantitative characterization of in-process control (IPC) samples generated during the fermentation and purification of the capsular polysaccharide (CPS), polyribosyl-ribitol-phosphate (PRP), derived from Hib. Reliable quantitative methods are necessary for all stages of production; otherwise accurate process monitoring and validation is not possible.

Physicochemical and immunochemical assays for monitoring consistent production of tetanus toxoid.

The detoxification of tetanus toxin by formaldehyde is a crucial step in the production of tetanus toxoid. The inactivation results in chemically modified proteins and it determines largely the ultimate efficacy and safety of the vaccine. Currently, the quality of tetanus toxoid lots is evaluated in potency and safety tests performed in animals.

Cysteine depletion causes oxidative stress and triggers outer membrane vesicle release by Neisseria meningitidis; implications for vaccine development.

Outer membrane vesicles (OMV) contain immunogenic proteins and contribute to in vivo survival and virulence of bacterial pathogens. The first OMV vaccines successfully stopped Neisseria meningitidis serogroup B outbreaks but required detergent-extraction for endotoxin removal. Current vaccines use attenuated endotoxin, to preserve immunological properties and allow a detergent-free process.

Identification and optimization of critical process parameters for the production of NOMV vaccine against Neisseria meningitidis.

Outer membrane vesicles (OMV) are used as a vaccine against Neisseria meningitidis serogroup B and are traditionally produced with detergent-extraction to remove toxic lipopolysaccharide. Engineered strains with attenuated lipopolysaccharide allowed the use of native vesicles (NOMV) with improved stability and immunogenicity. In the NOMV production process detergents are omitted and vesicle release is stimulated with EDTA extraction (a chelating agent) to enable a higher yield.

Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller.

This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer.

Improving the cellular pertussis vaccine: increased potency and consistency.

Although Europe, Canada and the US have switched from cellular to acellular pertussis vaccines, most developing countries will continue to use the more cost effective cellular vaccine. Consistency of production however is the typical problem inherent to cellular vaccines. Optimising the production process of cellular pertussis bulk suspensions using product potency as a measure is not possible, since the mandatory animal test to measure potency has little discriminatory power.

Fed-batch cultivation of Bordetella pertussis: metabolism and Pertussis Toxin production.

The production of acellular pertussis in comparison with whole cell pertussis vaccines demands 5-25 times the amount of Bordetella pertussis' virulence factors, such as Pertussis Toxin (PT), to produce the same number of vaccine doses. An increase in the volumetric productivity by employing fed-batch rather than the currently used batch cultivations of B. pertussis could reduce the cost price of acellular pertussis vaccines.

Effect of relevant culture parameters on Pertussis Toxin expression by Bordetella pertussis.

Whooping cough vaccines are produced using different ranges of cultivation conditions and medium compositions, which are known to influence growth rate, virulence factor production and degradation, as well as the virulence factors' association to the cell. This study quantifies the impact of individual parameters on Pertussis Toxin (PT) production, using an optimized chemically defined medium as starting point, rather than a complex medium. A number of chemicals that are identified affect both growth rate and virulence factor production, which occur at similar levels in various commonly used production media.

Rational medium design for Bordetella pertussis: basic metabolism.

In current Bordetella pertussis media ammonium accumulates because of an imbalance in the nitrogen:carbon ratio of the substrates used, which is one of the factors limiting cell density in fed-batch cultures. The aim of this study was to map B. pertussis catabolic and anabolic capabilities, in order to design a medium that avoids ammonium accumulation, while substrates are metabolised completely.

Quantification of cell-associated and free antigens in Bordetella pertussis suspensions by antigen binding ELISA.

In order to achieve batch-to-batch consistency of whole-cell pertussis vaccines, properties relevant for protection and safety should be characterised. Therefore, ELISAs to quantify pertussis toxin (PT), filamentous haemagglutinin (FHA), 92 kD outer membrane protein (92 kD-OMP) and pertactin (PRN) in Bordetella pertussis (B. pertussis) suspensions were developed.