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The study of polyamines transporter, PotD, as a vaccine antigen against Streptococcus pneumoniae

Grant number: 12/04286-3
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): May 01, 2012
Effective date (End): February 28, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Luciana Cezar de Cerqueira Leite
Grantee:Thiago Rojas Converso
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:08/05207-4 - Pneumococcal conjugate vaccine: capsular polysaccharide - pneumococcal surface protein A, AP.TEM


Streptococcus pneumoniae represents a serious risk to the world population's health, causes more than 1 million deaths every year, most of them in developing countries. The existing vaccines are based on capsular polysaccharides, and have high cost and/or low coverage; because of this, there are necessary investment in research for the development of alternatives vaccines approaches. The use of conserved proteins of pneumococcus has shown promise in several animal models; some of these proteins having tested in phase 1 clinical trials successfully. Among the most studied proteins as vaccine candidates against S. pneumoniae are the PSPA and pneumolysin or their derivatives; recent studies suggest PotD as a promising vaccine candidate. PotD is a protein that belongs to the PotABCD complex, which is an important complex that operates in the transport of polyamines from the outside to the intra-cellular environment. The Pot complex is present in virtually all strains of S. pneumoniae. The PotD is exposed on the bacterial surface and accessible to antibodies that can prevent the activity of polyamine carrier. The polyamines are essential for growth and survival in pneumococcal, which makes PotD a potential vaccine candidate. PspA is a virulence factor also exposed on the surface of bacteria, present in all isolates of S. pneumoniae and is able to protect mice against challenge with invasive pneumococcal virulence. Pneumolysin (Ply) is a conserved protein that has inflammatory property, besides interacting with TLR-4 and is directly involved in the innate immune response triggered by the pneumococcus. Since the ability to activate innate immunity is a characteristic of molecules with adjuvant properties, we postulate that Ply and/or PDT (mutated and in a non-toxic form), may have an adjuvant effect when used together with PspA and PotD, promoting a powerful immune response against both proteins. We propose to study PotD as vaccine antigen in combination with PdT and PspA against Pneumococcal Infection. (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)
CONVERSO, T. R.; GOULART, C.; DARRIEUX, M.; LEITE, L. C. C. A protein chimera including PspA in fusion with PotD is protective against invasive pneumococcal infection and reduces nasopharyngeal colonization in mice. Vaccine, v. 35, n. 38, p. 5140-5147, SEP 12 2017. Web of Science Citations: 5.
CONVERSO, T. R.; GOULART, C.; RODRIGUEZ, D.; DARRIEUX, M.; LEITE, L. C. C. Rational selection of broadly cross-reactive family 2 PspA molecules for inclusion in chimeric pneumococcal vaccines. Microbial Pathogenesis, v. 109, p. 233-238, AUG 2017. Web of Science Citations: 3.
CONVERSO, T. R.; GOULART, C.; RODRIGUEZ, D.; DARRIEUX, M.; LEITE, L. C. C. Systemic immunization with rPotD reduces Streptococcus pneumoniae nasopharyngeal colonization in mice. Vaccine, v. 35, n. 1, p. 149-155, JAN 3 2017. Web of Science Citations: 6.

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