New vaccine research based on recombinant proteins of dengue virus

• Grant number: 14/17595-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2015
• End date: November 30, 2017
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Luis Carlos de Souza Ferreira
• Grantee: Luis Carlos de Souza Ferreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Jaime Henrique Amorim Santos
• Associated research grant(s): 16/50496-0 - High-throughput generation of antigen binding fragments (Fabs) based on automated phage-display technology for diagnosis and treatment of Zika virus infection, AP.R SPRINT

Abstract

The present project aims the maintenance of ongoing studies dealing with new anti-dengue vaccine approaches at the Vaccine Development Laboratory (VDL) of the University of São Paulo. The scientific work will employ recombinant structural and non-structural proteins of type 2 dengue virus (DENV2), including the use of different domains of the envelope protein, NS1, NS3 and NS5, both expressed in heterologous systems. The vaccine formulations will be tested for the protective efficacy in a murine challenge model developed by our group using a DENV2 lineage naturally lethal to mice. The project team includes two PhD students and two under graduate students. Altogether, the proposal will encompass 2 specific research lines with the following main objectives: (i) identification of envelope protein epitopes involved in the generation of protective and non-protective antibodies; (ii) role of cellular immunity in the vaccine-induced protection by means of immunization with non-structural proteins (NS1, NS3 e NS5). The proposal shows different innovative aspects regarding the development of an effective anti-dengue vaccine and may have a significant impact in this field. (AU)

Scientific publications

(10)

(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)

ROCHA, LETICIA BARBOZA; DOS SANTOS ALVES, RUBENS PRINCE; CAETANO, BRUNA ALVES; PEREIRA, LENNON RAMOS; MITSUNARI, THAIS; AMORIM, JAIME HENRIQUE; POLATTO, JULIANA MOUTINHO; BOTOSSO, VIVIANE FONGARO; FRAZATTI GALLINA, NEUZA MARIA; PALACIOS, RICARDO; et al. Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies. ANTIBODIES, v. 6, n. 4, DEC 2017. (13/06589-6, 14/17595-0, 12/09096-8)

PEREIRA, LENNON RAMOS; DOS SANTOS ALVES, RUBENS PRINCE; SALES, NATIELY SILVA; ANDREATA-SANTOS, ROBERT; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; PEREIRA, SAMUEL SANTOS; CASTRO-AMARANTE, MARIA FERNANDA; RODRIGUES-JESUS, MONICA JOSIANE; DE PINHO FAVARO, MARIANNA TEIXEIRA; CHURA-CHAMBI, ROSA MARIA; et al. Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein. FRONTIERS IN MEDICAL TECHNOLOGY, v. 2, p. 14-pg., 2020-12-03. (14/17595-0, 16/20045-7, 16/23560-0, 18/14459-9, 16/05570-8, 18/08199-4, 17/09661-0, 16/14344-1)

PEREIRA, LENNON RAMOS; VICENTIN, ELAINE CRISTINA MATOS; PEREIRA, SARA ARAUJO; MAEDA, DENICAR LINA NASCIMENTO FABRIS; ALVES, RUBENS PRINCE DOS SANTOS; ANDREATA-SANTOS, ROBERT; SOUSA, FRANCIELLE TRAMONTINI GOMES DE; YAMAMOTO, MARCIO MASSAO; CASTRO-AMARANTE, MARIA FERNANDA; FAVARO, MARIANNA TEIXEIRA DE PINHO; et al. Intradermal Delivery of Dendritic Cell-Targeting Chimeric mAbs Genetically Fused to Type 2 Dengue Virus Nonstructural Protein 1. VACCINES, v. 8, n. 4, DEC 2020. (13/26942-2, 14/04303-0, 16/05570-8, 13/01702-9, 13/11442-4, 14/17595-0, 13/01690-0)

STAN, RAZVAN C.; FRANCOSO, KATIA S.; ALVES, RUBENS P. S.; FERREIRA, LUIS CARLOS S.; SOARES, IRENE S.; DE CAMARGO, MARISTELA M.. Febrile temperatures increase in vitro antibody affinity for malarial and dengue antigens. PLoS Neglected Tropical Diseases, v. 13, n. 4, APR 2019. (11/51778-6, 12/13032-5, 14/17595-0, 16/20045-7)

ANDREATA-SANTOS, ROBERT; DOS SANTOS ALVES, RUBENS PRINCE; PEREIRA, SARA ARAUJO; PEREIRA, LENNON RAMOS; DE FREITAS, CARLA LONGO; PEREIRA, SAMUEL SANTOS; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; CASTRO-AMARANTE, MARIA FERNANDA; PINHO FAVARO, MARIANNA TEIXEIRA; MATHIAS-SANTOS, CAMILA; et al. Transcutaneous Administration of Dengue Vaccines. Viruses-Basel, v. 12, n. 5, MAY 2020. (16/05570-8, 12/50362-3, 16/20045-7, 14/17595-0, 16/23560-0, 15/02352-7)

KANNO, ALEX ISSAMU; DE CERQUEIRA LEITE, LUCIANA CEZAR; PEREIRA, LENNON RAMOS; RODRIGUES DE JESUS, MONICA JOSIANE; ANDREATA-SANTOS, ROBERT; DOS SANTOS ALVES, RUBENS PRINCE; DURIGON, EDISON LUIZ; DE SOUZA FERREIRA, LUIS CARLOS; GONCALVES, VIVIANE MAIMONI. Optimization and scale-up production of Zika virus Delta NS1 in Escherichia coli: application of Response Surface Methodology. AMB EXPRESS, v. 10, n. 1, DEC 2020. (12/23124-4, 14/17595-0, 16/20045-7)

DOS SANTOS ALVES, RBENS PRINCE; PEREIRA, LENNON RAMOS; NASCIMENTO FABRIS, DENICAR LINA; SALVADOR, FELIPE SCASSI; SANTOS, ROBERT ANDREATA; DE ANDRADE ZANOTTO, PAOLO MARINHO; ROMANO, CAMILA MALTA; AMORIM, JAIME HENRIQUE; DE SOUZA FERREIRAA, LUIS CARLOS. Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen. Clinical and Vaccine Immunology, v. 23, n. 6, p. 460-469, JUN 2016. (15/02352-7, 12/21077-9, 14/17595-0)

ZANETI, ARTHUR BARUEL; YAMAMOTO, MARCIO MASSAO; SULCZEWSKI, FERNANDO BANDEIRA; ALMEIDA, BIANCA DA SILVA; SANTOS SOUZA, HIGO FERNANDO; FERREIRA, NATALIA SOARES; NASCIMENTO FABRIS MAEDA, DENICAR LINA; SALES, NATIELY SILVA; ROSA, DANIELA SANTORO; DE SOUZA FERREIRA, LUIS CARLOS; et al. Dendritic Cell Targeting Using a DNA Vaccine Induces Specific Antibodies and CD4(+) T Cells to the Dengue Virus Envelope Protein Domain III. FRONTIERS IN IMMUNOLOGY, v. 10, JAN 29 2019. (16/04477-4, 13/11442-4, 14/50631-0, 14/17595-0, 15/16565-2, 14/15061-8, 15/18874-2)

NASCIMENTO FABRIS MAEDA, DENICAR LINA; BATISTA, MILENE TAVARES; PEREIRA, LENNON RAMOS; CINTRA, MARIANA DE JESUS; AMORIM, JAIME HENRIQUE; MATHIAS-SANTOS, CAMILA; PEREIRA, SARA ARAUJO; BOSCARDIN, SILVIA BEATRIZ; SILVA, SANDRIANA DOS RAMOS; FAQUIM-MAURO, ELIANA L.; et al. Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein. FRONTIERS IN IMMUNOLOGY, v. 8, SEP 25 2017. (12/51204-2, 14/17595-0)

ALVES, RUBENS PRINCE DOS SANTOS; ANDREATA-SANTOS, ROBERT; DE FREITAS, CARLA LONGO; PEREIRA, LENNON RAMOS; FABRIS-MAEDA, DENICAR LINA NASCIMENTO; RODRIGUES-JESUS, MONICA JOSIANE; PEREIRA, SAMUEL SANTOS; CARVALHO, ALEXIA ADRIANNE VENCESLAU BRITO; SALES, NATIELY SILVA; PERON, JEAN PIERRE SCHATZMANN; et al. Protective Immunity to Dengue Virus Induced by DNA Vaccines Encoding Nonstructural Proteins in a Lethal Challenge Immunocompetent Mouse Model. FRONTIERS IN MEDICAL TECHNOLOGY, v. 2, p. 12-pg., 2020-10-30. (17/26170-0, 14/17595-0, 15/02352-7, 12/21077-9)

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