Development of a vaccine strategy against Shiga toxin of enterohemorrhagic Escherichia coli (EHEC) based recombinant protein Stx2AB incorporated into liposomes

• Grant number: 14/21141-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2015
• End date: October 31, 2016
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luis Carlos de Souza Ferreira
• Grantee: Mônica Josiane Rodrigues de Jesus
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

This project aims to develop a vaccine strategy for prophylactic against haemolytic uremic syndrome (HUS), the most severe sequelae associated with infection by strains of enterohaemorrhagic Escherichia coli (EHEC). The disease is directly associated with the production of the toxin Stx2, particularly by EHEC strains of serotype O157: H7. The proposal is based on a formulation comprised of a non-toxic recombinant form of Stx2, the Stx2AB (previously obtained by containing group and the B subunit plus 31 amino acids of the A2) incorporated into liposomal vesicles. The work involves the evaluation of immunogenic properties and vaccine protective potential of different formulations tested in an experimental model. For this, the purified protein will be incorporated into the multilamellar lipid vesicles and administered to mice after the administration by the parenteral route. The humoral anti-Stx2AB will be monitored by ELISA assays (serum IgG anti-Stx2AB, sub-classes of IgG). Also will be tested the effects of neutralizing antibodies generated against the native toxin (cytotoxicity in Vero cells and in mice) protective e immunity measured by survival challenge with the toxin and control of serum urea and creatinine. The research to be done is relevant contribution to scientific knowledge in the area and may open perspectives for vaccine control of HUS. (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)

BARBOSA, CARLA M.; DI PAOLA, NICHOLAS; CUNHA, MARIELTON P.; RODRIGUES-JESUS, MONICA J.; ARAUJO, DANIELLE B.; SILVEIRA, VANESSA B.; LEAL, FABYANO B.; MESQUITA, FLAVIO S.; BOTOSSO, VIVIANE F.; ZANOTTO, PAOLO M. A.; et al. Yellow Fever Virus RNA in Urine and Semen of Convalescent Patient, Brazil. Emerging Infectious Diseases, v. 24, n. 1, p. 176-178, JAN 2018. (14/17766-9, 14/21141-4, 16/08727-5, 13/22136-1, 16/08204-2)

RODRIGUES-JESUS, M. J.; FOTORAN, W. L.; CARDOSO, R. M.; ARAKI, K.; WUNDERLICH, G.; FERREIRA, LUIS C. S.. Nano-multilamellar lipid vesicles (NMVs) enhance protective antibody responses against Shiga toxin (Stx2a) produced by enterohemorrhagic Escherichia coli strains (EHEC). Brazilian Journal of Microbiology, v. 50, n. 1, p. 67-77, JAN 2019. (14/21141-4, 15/17174-7)

Academic Publications

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

JESUS, Mônica Josiane Rodrigues de. Development of a vaccine strategy against Shiga toxin (Stx) of Escherichia coli (EHEC) based on recombinant protein Stx2ΔAB incorporated into liposomes.. 2017. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.