Anti-pneumococcal vaccines based on PSPA, pneumolysin and polysaccharides: immune response and protection against sepsis in mice

• Grant number: 09/03088-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2009
• End date: November 30, 2011
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Michelle Darrieux Sampaio Bertoncini
• Grantee: Michelle Darrieux Sampaio Bertoncini
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Streptococcus pneumoniae is a major cause of pneumonia, meningitis ad sepsis. The high cost and limited coverage of the current conjugate vaccine, containing PS from 7 prevalent serotypes, reinforce the need for a more cost-effective vaccine, with wide coverage. Several pneumococcal proteins have been studied as vaccina candidates, of which pneumolysin (Ply) and PspA have shown the most promising results in sepsis animal models. The combination of these 2 proteins induced the highest protection in mice, combining the high imunogenicity of PspA and the adjuvan effect of Ply. BAsed on those results, the present project involves the obtention of hybrid proteins containing fusions of the N-terminus of PspA and the mutated Ply gene. These fusions will be purified as single antigens, reducing the production costs. The fusions will be evaluated os for antibody and citokynes production, as well as protection against pneumococcal challenge. The fusions should also be conjugates to polysaccharides (PS), broadening its immunogenicity and coverage. These formulations will be evaluated as for the induced immune response and protection potential in animal models of pneumococcal sepsis, and will contribute significantly to the understanding of the mechanisms of imune protection against pneumococci. (AU)