A new way for the rational pursuit of an effective vaccine against dengue

• Grant number: 12/51204-2
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2013
• Effective date (End): November 29, 2015
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Luis Carlos de Souza Ferreira
• Grantee: Jaime Henrique Amorim Santos
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 14/00684-0 - Structural mapping of key epitopes on the envelope of dengue virus with regard to neutralization and antibody-dependent enhancement, BE.EP.PD

Abstract

Dengue is a disease of high epidemiological impact caused by one of the four serotypes of dengue virus (DV 1-4). There is still no effective and safe vaccine for the control of this disease. One of the main problems that hinder the development of this vaccine is the lack of knowledge about cellular and molecular mechanisms which are involved in the protective immunity against DV. The protective immune response exists, since a previous infection with a specific DV serotype confers immunity to a subsequent contact with viruses of the same serotype. The main objective of this research project is to determine which cellular and molecular mechanisms are involved in the protective immunity against dengue. The research strategy is to induce, in a murine model, a non-lethal infection capable of inducing protection against a subsequent lethal infection. Then, we hope to evaluate the molecular and cellular mechanisms involved in the protective immune response using all the DV type 2 antigens available in our laboratory (prM, E, NS1, NS3, NS5). Thus, we expect to understand and determine which of these mechanisms are essential in a protective immune response against DV. The knowledge generated from this research will optimize the design of vaccine formulations against dengue, increasing the chances of success in the search for an effective vaccine. The challenges are immense, after three decades of research, largely subsidized by larger laboratories producing vaccines in the world, there is still not yet an effective vaccine against dengue. For all perspectives of results mentioned above, we believe that this project has great relevance and can benefit both the scientific community involved with the issue and the society in general. (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)

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.; SILVEIRA, VANESSA BARBOSA; LEAL OLIVEIRA, DANIELLE BRUNA; JOHNSTON, STEPHEN ALBERT; DE SOUZA FERREIRA, LUIS CARLOS; RODRIGUES, JULIANA FALCAO. Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein. FRONTIERS IN IMMUNOLOGY, v. 8, SEP 25 2017. Web of Science Citations: 4.

AMORIM, JAIME HENRIQUE; DOS SANTOS ALVES, RUBENS PRINCE; BIZERRA, RAIZA; PEREIRA, SARA ARAUJO; PEREIRA, LENNON RAMOS; NASCIMENTO FABRIS, DENICAR LINA; SANTOS, ROBERT ANDREATA; ROMANO, CAMILA MALTA; DE SOUZA FERREIRA, LUIS CARLOS. Antibodies are not required to a protective immune response against dengue virus elicited in a mouse encephalitis model. VIROLOGY, v. 487, p. 41-49, JAN 2016. Web of Science Citations: 8.

SALVADOR, FELIPE SCASSI; AMORIM, JAIME HENRIQUE; SANTOS ALVES, RUBENS PRINCE; PEREIRA, SARA A.; SOUZA FERREIRA, LUIS CARLOS; ROMANO, CAMILA MALTA. Complete Genome Sequence of an Atypical Dengue Virus Serotype 2 Lineage Isolated in Brazil. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 3, n. 4 JUL-AUG 2015. Web of Science Citations: 1.