Multi-peptide vaccine to confer serotype-independent protection against pneumonia. (FAPESP-RCUK MRC)

Resumo

The development of a vaccine based on "common pneumococcal proteins" offers the potential for serotype-independent protection overcoming the problem of serotype replacement that emerged after pneumococcal conjugate vaccine widespread use. Researchers at the Butantan Institute have been evaluating the pneumococcal antigens PspA and PspC as vaccine candidates. Although these proteins are variable among different clinical isolates, some variants are able to induce antibodies with broad reactivity, that recognise different PspA and PspC variants. We aim to determine the epitopes (parts of the protein) that are targeted by these broad-reacting sera in mice immunized with different fragments of these proteins and further in human serum of healthy adults and pneumonia patients. Samples from adults exposed during an experimental colonization model will provide information on peptides that are recognized during natural exposure to the bacteria and therefore are important for the natural acquired immunity that protects adults against pneumonia. Based on mice and human data we will select broad-reactive epitopes and construct a multiple-epitope protein. Cross-reactivity of serum will be assessed in ELISAs and Western Blots and cross-protection in animal models using pneumococcal strains expressing different PspA and PspC variants. Finally we will assess if serum and brochoalveolar lavage from patients with pneumonia (elderly) present lower levels of antibodies against the multiple-epitope protein compared to healthy adults and therefore their susceptibility to the disease. (AU)