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Development of protein vaccines against Streptococcus pneumoniae: characterization of the adjuvant components characterization of the cellular pertussis vaccine and analysis ze of new vaccine combinations

Grant number: 12/10593-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2012
Effective date (End): June 30, 2015
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal researcher:Maria Leonor Sarno de Oliveira
Grantee:Carolina Salcedo Rivillas
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Streptococcus pneumoniae is responsible for killing nearly one million of children under 5 years old every year, in the worldwide. Vaccines based on protein antigens are alternatives to commercial vaccines available for S. pneumoniae, that consisting of capsular polysaccharide and presenting some disadvantagesdisadvantagedrawbacks related to production costs and serotype coverage. Our group recently presented a proposal for a vaccine based on the PspA antigen (Pneumococcal surface protein A) using the cellular pertussis vaccine (wP) as adjuvant. Since wP is an approved vaccine for Brazilian children above two months years old children in Brazil, as part of the triple DTP triple formulation vaccine (diphtheria, tetanus and pertussis), our proposal might open doors for result in a quadruple composition, taking advantage of the an adjuvant action of a component already administered to approved for use in children. The combination PspA5-wP conferred protection in animal models of pneumococcal challenge. Our studies also indicated that the LPS of Bordetella pertussis is not a determinant component of the adjuvant action observed. and Tthus, other components of B. pertussis should be acting as an adjuvant in this model. In this project we propose to characterize the molecular and immunomodulatory basis of the adjuvant activity of B. pertussis in combination with pneumococcal antigens in mice. For this, by the use of mutants of B. pertussis that are deficient in one or more components having with known immunomodulatory properties known or , besides purified components will be used. The characterization of the adjuvant activityon is important, as new pertussis vaccines formulation are being presentedproposed to different populations. Furthemore, in alternative to the pertussis vaccine, we propose the evaluation of the adjuvant properties of the BCG vaccine in combination with PspA antigen of S. pneumoniae, for a formulation that couldwich might be administered toused by newborn infants.