ABSTRACT Haemophilus influenzae type b (Hib) vaccine is made up from its capsular polysaccharide (PRP). Low productivity of the polysaccharide during cell growth increases the final cost of this vaccine. Hib achieves low levels of cellular concentration in vitro due to the inhibition caused by acetate. The Akaike Information Criterion (AIC) was used in this work for selecting models of microbial growth. The application to the case of the multivariate models is outlined and the procedure is carried out using data from Hib cultures. From 4 models of biomass and 15 of acetate and PRP, one could be selected with great evidence for support. The use of AIC has shown to be robust and free of subjectivity, and it was able to define a kinetic model that is adequate for the cell growth and the production of its PRP over a wide range of culture conditions. The exponential inhibition factor was found to be the best for modelling inhibition of cell growth by acetate, while the hyperbolic factor was the best for inhibition of PRP formation. The acetate formation was found to have both growth associated and non-associated types. PRP formation was found to be only growth associated.

Flagellin is the structural protein and most abundant component of bacterial flagella. The flagellum filament contains around 20,000 - 100,000 subunits of 50 kDa flagellin that can have diverse biotechnological applications such as vaccine adjuvant and cellular protector during chemo- and radiotherapy. The main aim of this work was to study a production process of purified native FliC flagellin of Salmonella Typhimurium. The culture conditions in shakers were established with medium devoid of animal-derived components. In bioreactors, culture conditions were established in order to obtain flagellin from the culture supernatant by tangential ultrafiltration (TUF). The concentrated 750 kDa cut-off TUF fraction had a purification factor of 1.5 and a recovery yield of 52.2% for flagellin. The volumetric production of flagellin using the described procedure achieved around 307 mg/L of culture, which represented a significant improvement over previously reported methods. These results permit the development of production and purification processes that can be easily scaled up.