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Bacillus subtilis as a platform for mucosal vaccines development against human dental caries

Grant number: 12/51189-3
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): February 01, 2013
Effective date (End): July 31, 2016
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Rita de Cássia Café Ferreira
Grantee:Milene Tavares Batista
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):15/15562-0 - Characterization of the immunosignature of the antibodies produced after a mucosal vaccination strategies in mice against human dental caries, BE.EP.PD


There is no vaccine against dental caries on the market and the lack of appropriate antigens and delivery mucosal vectors are among the main reason for such situation. B. subtilis is used as expression system of heterologous proteins and as vaccine vehicle administered by mucosal routes. This project aims the development of genetically modified B. subtilis strains as a platform for the development of mucosal vaccines against dental caries. Recent discoveries achieved by the applicant and the research group at USP opened renewed perspectives for the development of effective anti-caries-vaccines and will constitute the aim and motivation of the post-doctorate project. The work will be divided in three parts: i) development of vaccine formulations based on recombinant antigens of S. mutans produced in B. subtilis strains in combination with an adjuvant; ii) developing of vaccines based on recombinant B. subtilis spores as delivery vehicles of immunomodulators and S. mutans antigens; iii) assessment of vaccine efficacy using a murine caries model. As vaccine antigens we will use different structural and functional domains of the protein P1, the most important S.mutans antigen, the protein GbpB and a hybrid protein encompassing both a P1 fragment and GbpB. The antigens will be administered via mucosal (oral and sublingual) in association with a mucosal adjuvant. The research will also evaluate a new delivery system based on spores of B. subtilis modified to amplify and modulate immune responses directed to S. mutans antigens. The efficacy of different vaccine formulations will be determined by the production of systemic and secreted antigen-specific antibodies and generation of protective immunity using a cariogenic S. mutans strain in a murine model recently established in the lab. The proposed research is original and innovative and should contribute to the development of effective vaccines against dental caries. (AU)

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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)
BATISTA, MILENE TAVARES; FERREIRA, EWERTON LUCENA; PEREIRA, GISELA DE SOUZA; STAFFORD, PHILLIP; NASCIMENTO FABRIS MAEDA, DENICAR LINA; RODRIGUES, JULIANA FALCAO; BRADY, L. JEANNINE; JOHNSTON, STEPHEN ALBERT; DE SOUZA FERREIRA, LUIS CARLOS; CAFE FERREIRA, RITA DE CASSIA. LT adjuvant modulates epitope specificity and improves the efficacy of murine antibodies elicited by sublingual vaccination with the N-terminal domain of Streptococcus mutans P1. Vaccine, v. 35, n. 52, p. 7273-7282, . (15/15562-0, 12/51189-3, 13/06671-4)
BATISTA, MILENE TAVARES; SOUZA, RENATA D.; FERREIRA, EWERTON L.; ROBINETTE, REBEKAH; CROWLEY, PAULA J.; RODRIGUES, JULIANA F.; BRADY, L. JEANNINE; FERREIRA, LUIS C. S.; FERREIRA, RITA C. C.. Immunogenicity and In Vitro and In Vivo Protective Effects of Antibodies Targeting a Recombinant Form of the Streptococcus mutans P1 Surface Protein. Infection and Immunity, v. 82, n. 12, p. 4978-4988, . (12/51189-3, 13/06671-4)

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Filed patent(s) as a result of this research project

ESPOROS DE BACILLUS SP., MÉTODO DE PREPARO DOS ESPOROS, MÉTODO DE PREPARO DE CARTUCHOS DE BIOBALiSTICA, E USOS DOS ESPOROS BR1020140096795 - Universidade de São Paulo (USP) . Julio Kravcuks Rozenfeld ; Luana Raposo de Moraes Aps ; Luis Calos de Souza Ferreira ; Maria Teresa Moura Maly ; Mariana de Oliveira Diniz ; Milene Tavares Batista - April 2014, 23