Adenylate cyclase toxin from Bordetella pertussis as an antigen presentation system for the PspA antigen from Streptococcus pneumoniae: characterization of immune responses and protection in mice

Abstract

Streptococcus pneumoniae (pneumococcus) colonizes the upper respiratory tract of healthy individuals, establishing a commensal relationship with the host. Occasionally, pneumococcus may invade normally sterile sites causing diseases such as pneumonia, septicemia, meningitis, otitis media, and sinusitis. Annually, pneumococcus is responsible for the death of about 400,000 children under the age of 5 worldwide. Commercially available vaccines are composed of polysaccharides of the prevalent serotypes and protection is limited to the serotypes present in the formulations. Our group has been working on the development of pneumococcal vaccines composed of protein antigens in order to obtain formulations able to provide broad protection against serotypes. Pneumococcus Surface Protein A (PspA) is among the most promising antigens. Recently, in collaboration with Dr. Daniel Ladant's group from Pasteur Institute of Paris, our group tested an antigen presentation system based on the adenylate cyclase toxin from Bordetella pertussis for the presentation of PspA fragments (CyaA-PspA) to the immune system, through mouse immunization experiments. Initial results showed that the system is promising since it has shown adjuvant activity when compared to the PspA fragments alone, inducing high levels of antibodies and protection against invasive challenges with pneumococcal strains expressing homologous PspAs. Continuing the work, we propose in this project, the characterization of these vaccine candidates regarding the type of immune response and the ability to induce broad protection against different pneumococcal isolates, as well as protection against nasal colonization. (AU)