Pneumococcal whole-cell vaccine: optimization of cell growth of unencapsulated <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis> in bioreactor using animal-free medium |
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Authors: | C Liberman M Takagi J Cabrera-Crespo M E Sbrogio-Almeida W O Dias L C C Leite V M Gonçalves |
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Institution: | 1.Centro de Biotecnologia,Instituto Butantan,S?o Paulo,Brazil |
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Abstract: | The high cost of the available pneumococcal conjugated vaccines has been an obstacle in implementing vaccination programs
for children in developing countries. As an alternative, Malley et al. proposed a vaccine consisting of inactivated whole-cells
of unencapsulated S. pneumoniae, which provides serotype-independent protection and involves lower production costs. Although the pneumococcus has been extensively
studied, little research has focused on its large-scale culture, thus implying a lack of knowledge of process parameters,
which in turn are essential for its successful industrial production. The strain Rx1Al− eryR was originally cultured in Todd–Hewitt medium (THY), which is normally used for pneumococcus isolation, but is unsuitable
for human vaccine preparations. The purposes of this study were to compare the strains Rx1Al− eryR and kanR, develop a new medium, and generate new data parameters for scaling-up the process. In static flasks, cell densities were
higher for eryR than kanR. In contrast, the optical density (OD) of the former decreased immediately after reaching the stationary phase, and the OD
of the latter remained stable. The strain Rx1Al− kanR was cultivated in bioreactors with medium based on either acid-hydrolyzed casein (AHC) or enzymatically hydrolyzed soybean
meal (EHS). Biomass production in EHS was 2.5 times higher than in AHC, and about ten times higher than in THY. The process
developed for growing the strain Rx1Al− kanR in pH-controlled bioreactors was shown to be satisfactory to this fastidious bacterium. The new culture conditions using
this animal-free medium may allow the production of the pneumococcal whole-cell vaccine. |
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Keywords: | Pneumococcal whole-cell vaccine Streptococcus pneumoniae culture conditions Culture medium development |
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