Gene-expression-based quality scores indicate optimal harvest point in Bordetella pertussis cultivation for vaccine production.

The evolution of vaccine product quality during batch cultivation of Bordetella pertussis, the causative agent of whooping cough, was investigated with the goal to determine the optimal harvest point. The process was explored by measuring mRNA expression at frequent intervals during cultivation. The genes that are involved in virulence are already known for this product and changes in their expression levels are proposed to be indicative for product quality.

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.

Advanced process monitoring: the ultimate alternative.

Parametric release has the possibility to be the ultimate alternative for the use of animal tests. It involves the release of a product using evaluation of tightly controlled physical parameters, without the performance of a test on the final product. This practice is strengthened if there is a lack of validity for the final test to indicate quality or consistency.

Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice.

In this study, the ability of chitosan microparticles to enhance both the systemic and local immune responses against diphtheria toxoid (DT) after oral and nasal administration in mice was investigated.Firstly, DT was associated to chitosan microparticles to determine antigen loading and release. Then DT loaded chitosan microparticles, DT in phosphate buffered saline (PBS) and empty chitosan microparticles (as controls) were fed intragastrically and administered nasally to mice.

Dual-substrate utilization by Bordetella pertussis.

To improve the cultivation of Bordetella pertussis and take advantage of the newest techniques in monitoring and control, a quantitative description of substrate utilisation is necessary. Growth of the organism is limited by two main substrates. However neither interactive nor non-interactive modelling seem appropriate.

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.

Antigenic and immunogenic properties of inactivated polio vaccine made from Sabin strains.

Inactivated polio vaccine (IPV) was prepared with the Sabin strains, normally used for the attenuated live vaccine. The vaccine was characterized with respect to its antigenicity as determined by ELISA and biosensor analysis and its immunogenicity in rats. Compared with the vaccine prepared with virulent strains (Mahoney, MEF and Saukett) some distinct differences were found with regard to the interaction with glass vials (types 1 and 2) and antigenicity (type 3).

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.

Comparison of enhanced potency inactivated poliovirus vaccine (EIPV) versus standard oral poliovirus vaccine (OPV) in Thai infants.

Enhanced potency inactivated poliovirus vaccine (EIPV), combined with diphtheria-tetanus-pertussis (DTP) vaccine, was compared with oral poliovirus vaccine (OPV) regarding immunogenicity in Thai infants, vaccinated at 2, 4 and 6 months of age. EIPV induced significantly higher seroconversion rates than OPV to all 3 poliovirus types after the second and third immunization. After 3 doses of each vaccine, at 7 months of age, all infants receiving EIPV proved seropositive for poliovirus type 1, type 2 and type 3 neutralizing antibodies, whereas of those receiving OPV, 9% remained seronegative (titre < 1:4) for type 1 (p = 0.