Development of a vaccine against Streptococcus pneumoniae and Bordetella pertussis

Abstract

Streptococcus pneumoniae (pneumococcus) is a major cause of pneumonia, meningitis and systemic infections in children worldwide. Recent estimates calculate that between 700,000 and 1 million people die each year from infections caused by S. pneumoniae around the world. The pneumococcal surface protein A (PspA) is a well characterized antigen which confers protection in animal models, representing a good alternative to current conjugate vaccines. Induction of protective immune response directed to PspA in animal models has been described, but few inexpensive adjuvants for the composition of a subunit vaccine have been proposed to date. Recently, our group has tested the adjuvant properties of the cellular pertussis vaccine (wP) produced by Instituto Butantan, as adjuvant in combination with PspA. The wP vaccine is one of the components of the triple vaccine DTP (diphtheria, tetanus, pertussis ) provided to Brazilian children by the Ministry of Health, at 2, 4 and 6 months of age, with boosters at 18 months and five years . This vaccine is highly effective against the three diseases. Nasal immunization of BALB /c mice with a combination of PspA and wP, induced high levels of anti- PspA antibodies and conferred protection against lethal infections as well as nasal colonization by S. pneumoniae. Similarly, the DTP vaccine also had adjuvant effect when combined with PspA, leading to protection of vaccinated animals against lethal challenges different pneumococcal strains. These studies also demonstrated that PspA vaccines do not interfere with the response to the DTP components, showing that the inclusion of PspA on the DTP vaccine is a promising strategy. In this project, we propose the expression of PspA in the B. pertussis vaccine strain, in order to produce an inactivated recombinant vaccine wPPspA. The advantage of this strategy is the production of a vaccine formulation against pertussis and pneumococcus by the fermentation and inactivation of a recombinant B. pertussis, thus eliminating the current stages to obtain PspA, which involve the expression in Escherichia coli and purification of the recombinant protein. The immune response and protection against pneumococcus and pertussis induced in animals vaccinated with wPPspA will be assessed. (AU)