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Multi-peptide vaccine to confer serotype-independent protection against pneumonia

Grant number: 12/50816-4
Support type:Regular Research Grants
Duration: March 01, 2013 - February 28, 2015
Field of knowledge:Biological Sciences - Immunology
Cooperation agreement: MRC, UKRI
Principal Investigator:Eliane Namie Miyaji
Grantee:Eliane Namie Miyaji
Principal investigator abroad: Stephen Brian Gordon
Institution abroad: Liverpool School of Tropical Medicine (LSTM), England
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

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)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VADESILHO, CINTIA F. M.; FERREIRA, DANIELA M.; GORDON, STEPHEN B.; BRILES, DAVID E.; MORENO, ADRIANA T.; OLIVEIRA, MARIA LEONOR S.; HO, PAULO L.; MIYAJI, ELIANE N. Mapping of Epitopes Recognized by Antibodies Induced by Immunization of Mice with PspA and PspC. Clinical and Vaccine Immunology, v. 21, n. 7, p. 940-948, JUL 2014. Web of Science Citations: 11.

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