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Vaccine against Streptococcus pneumoniae based on choline-binding proteins

Grant number: 11/06583-2
Support type:Regular Research Grants
Duration: October 01, 2011 - September 30, 2013
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Eliane Namie Miyaji
Grantee:Eliane Namie Miyaji
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Streptococcus pneumoniae is an important human pathogen, causing diseases such as meningitis, pneumonia, bacteremia and sepsis. The vaccines currently available are effective and based on the response against the capsular polysaccharide, but they have some drawbacks such as high cost and coverage limited to the serotypes included in the vaccine formulation. The 7-valent polysaccharide conjugate vaccine led to a drastic reduction in the infections caused by vaccine serotypes, but there was also a rapid increase in disease caused by non-vaccine serotypes. The development of new vaccines against pneumococcal infections thus continues to be a priority. Several recombinant proteins expressed in Escherichia coli are being studied as vaccine antigens, including PspA (Pneumococcal surface protein A) and PspC (Pneumococcal surface protein C). Pneumococci have several proteins that are bound to the surface of the bacteria through interaction with choline present in the lipoteichoic acic from the cell membrane or teichoic acid from the cell wall, known as choline-binding proteins (CBPs). PspA and PspC are among the most important CBPs. This project aims at evaluating CBPs purified directly from S. pneumoniae cultures as vaccine formulation. Bacteria grown in chemically defined medium without choline and with ethanolamine do not retain CBPs on their surface and these proteins are released to the culture supernatant. We thus propose the use of CBPs purified from the culture supernatant from the non-encapsulated isolate Rx1 as a vaccine formulation, which will be evaluated in mice using models of colonization and intranasal lethal challenges. A vaccine based on CBPs would provide broad coverage, since it would be composed of a mixture of different pneumococcal antigens. (AU)