Optimization of the Production of Inactivated Clostridium novyi Type B Vaccine Using Computational Intelligence Techniques

Abstract

Clostridium novyi causes necrotic hepatitis in sheep and cattle, as well as gas gangrene. The microorganism is strictly anaerobic, fastidious, and difficult to cultivate in industrial scale. C. novyi type B produces alpha and beta toxins, with the alpha toxin being linked to the presence of specific bacteriophages. The main strategy to combat diseases caused by C. novyi is vaccination, employing vaccines produced with toxoids or with toxoids and bacterins. In order to identify culture medium components and concentrations that maximized cell density and alpha toxin production, a neuro-fuzzy algorithm was applied to predict the yields of the fermentation process for production of C. novyi type B, within a global search procedure using the simulated annealing technique. Maximizing cell density and toxin production is a multi-objective optimization problem and could be treated by a Pareto approach. Nevertheless, the approach chosen here was a step-by-step one. The optimum values obtained with this approach were validated in laboratory scale, and the results were used to reload the data matrix for re-parameterization of the neuro-fuzzy model, which was implemented for a final optimization step with regards to the alpha toxin productivity. With this methodology, a threefold increase of alpha toxin could be achieved.

Vaccine Production to Protect Animals Against Pathogenic Clostridia

“…TcnA is encoded within a prophage genome in both C. novyi toxinotypes [257]. This bacteriophage is believed to regulate toxin production and morphology [258,259,260]. Moreover, homologous genes or a novel C. perfringens toxin regulator (CPE1446-CPE1447) [261] and an AgrD quorum sensing peptide (Cno-19402) [7] are found in C. novyi.…”

“…C. novyi is grown for 18 to 72 h at 37 °C and inactivation of TcnA is achieved by incubation with 0.4% formalin at 37 °C for three days [227]. A more recent study showed that modeling the difficult C. novyi fermentation process using computational tools allowed optimization of toxin productivity, cell density, and fermentation time [260].…”

Rapid Tests for Detection of Main Clostridial Toxins

“…1) In cattle the way to prevent this disease is vaccination, employing vaccines produced with toxoids or with toxoids and bacterins [17,[130][131][132].…”

“…The standardization of culture in industrial reactors is complex, since the release of toxin into the medium is quite erratic between batches, starting and reaching its peak at different times [130,133]. At present, toxin concentration is measured by using in vivo methods by means of experimental animals, which have clear drawbacks.…”

Determination Model of Tectonic Seismicity Level In Earthquake Early Warning System By Implementing ANFIS (Adaptive Neuro Fuzzy Inference Systems)

“…the data acquisition analysis for multiple sensors using modulation frequency with telemetry technique can be done. [5]In addition, ANFIS is also widely used in various researches, such as the use of ANFIS for the stability of single machine power output [6] and multi engine [7], broiler cage temperature setting [8], color clashing on ancient inscriptions [9], for Short-Term Load Forecasting [10], Evaluation of Flashover Voltage Levels of Contaminated Hydrophobic Polymer Insulators [11], for determination of PH value [12], to detect breast cancer [13], determination of river flow direction [14], Optimization of the Production of Inactivated Clostridium novyi Type B Vaccine [15], Quantitative Structure-Activity Relationship Model for HCVNS5B inhibitors based on an Antlion [16] determination of forecasting volcanic eruption [17], density prediction for long term wind power [18], prediction water quality index of Satluj river in India [19]. To predict the seismic strength level cannot be predicted certainty by stochastic method.…”