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J. Infect. Dis. Ther., 1(3), p. 8-20

DOI: 10.14205/2310-9386.2015.03.01.2

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Assessment of the Bordetella pertussis BpCNIC0311 Strain as a Producing Strain of Genetically Detoxified Toxoid (PTg), Filamentous Hemagglutinin (FHA) and Type 2 Pertactin (Prn2)

This paper is available in a repository.
This paper is available in a repository.

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Abstract

Pertussis is a vaccine preventable disease caused by the Gram-negative bacterium Bordetella pertussis (B. pertussis). Acellular vaccines as regard to whole cell vaccines are less reactogenic and very similar in efficacy. An increased incidence of B. pertussis infections in countries where acellular vaccines are widely used has questioned their effectiveness. In fact, the circulating strains differ from vaccine strains due to variations in protein sequences associated to the evolutionary process of B. pertussis. Furthermore, vaccine antigens change throughout the manufacturing process caused by chemical treatments for toxin inactivation. Both aspects should be considered when looking into the loss of efficacy of acellular vaccines. In this paper we study the performance of a new producing strain, BPCNIC0311. The strain expresses the genetically inactivated pertussis toxoid (PTg) and type 2 pertactin (Prn2), the most frequently occurring pertactin variant in clinical isolates. As a result, the new strain is able to grow stably at high cell density in a chemically defined culture medium. Similarly, the strain stably expresses high levels of PTg, FHA and Prn2 antigens which allow for suitable yields after purification. High purity and adequate physicochemical features of the antigens were obtained. The three components formulated in alum, as a stand-alone pertussis preparation, were highly immunogenic and induced a protective immune response in mice against the reference strain BP18323. It is concluded that the new strain can be used to obtain sufficient amounts of PTg, FHA and Prn2 for preclinical studies of an improved-updated acellular vaccine against whooping cough.