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

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

Abstract

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

(4)

(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, THIAGO ROJAS; GOULART, CIBELLY; RODRIGUEZ, DUNIA; SOUZA GUERRA, MARIA EDUARDA; DARRIEUX, MICHELLE; LEITE, LUCIANA C. C.. Immune response induced in mice by a hybrid rPotD-PdT pneumococcal protein. PLoS One, v. 17, n. 8, p. 14-pg., 2022-08-22. (12/04286-3, 17/24832-6, 19/23566-6)

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. (12/04286-3)

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. (12/04286-3)

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. (12/04286-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CONVERSO, Thiago Rojas. The study of the polyamine transporter, PotD, and it hybrids as vaccine antigens against Streptococcus pneumoniae.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.