Recombinant Vaccines against Streptococcus pneumoniae and Bordetella pertussis

Abstract

Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia, meningitis and generalized infections worldwide. Recent estimates calculate that approximately 500,000 children under 5 die every 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 the present conjugate vaccines. Induction of protective immune response directed to PspA in animal models has been described, however, few low cost adjuvants for the composition of a subunit vaccine, have been proposed to date. Our group has tested the adjuvant properties of the whole cell pertussis vaccine (wP) produced at the Butantan Institute, as an adjuvant in combination with PspA. The wP vaccine is one of the components of the triple DTP (diphtheria, tetanus, pertussis) provided to Brazilian children by the Ministry of Health, at 2, 4 and 6 months of age with a booster 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 a lethal challenges and a nasal colonization by S. pneumoniae. Similarly, DTP vaccine also had an adjuvant effect when combined with PspA, leading to protection of vaccinated animals against lethal challenges with pneumococci. The study also demonstrated that PspA does not interfere with the response to the DTP antigens, showing that the inclusion of PspA in the DTP vaccine is a promising strategy. In this project, we propose the study of two new vaccine strategies. The first is the expression of PspA in the vaccine strain of B. pertussis in order to produce an inactivated recombinant vaccine wPPspA. The advantage of this strategy is the production of a dual formulation against pertussis and pneumococcal infections by fermentation of a recombinant B. pertussis, eliminating the current step of obtaining the PspA involving the expression in Escherichia coli and purification of the protein. The second is the use of an antigen presentation system based on the adenylate cyclase toxin of B. pertussis. This toxin has the capacity to bind to receptors present on antigen presenting cells and may direct the presentation of PspA to the immune system and modulate the response to this protein. (AU)