Dendritic Cell Targeting Using a DNA Vaccine Induces Specific Antibodies and CD4(+) T Cells to the Dengue Virus Envelope Protein Domain III

Author(s):Show less -

Zaneti, Arthur Baruel ^[1] ; Yamamoto, Marcio Massao ^[1] ; Sulczewski, Fernando Bandeira ^[1] ; Almeida, Bianca da Silva ^[1] ; Santos Souza, Higo Fernando ^[1] ; Ferreira, Natalia Soares ^[1] ; Nascimento Fabris Maeda, Denicar Lina ^[2] ; Sales, Natiely Silva ^[2] ; Rosa, Daniela Santoro ^{[3, 4]} ; de Souza Ferreira, Luis Carlos ^[2] ; Boscardin, Silvia Beatriz ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[3] Fed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[4] Iii INCTiii, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 10, JAN 29 2019.
• Web of Science Citations: 3

Abstract

Dengue fever has become a global threat, causing millions of infections every year. An effective vaccine against all four serotypes of dengue virus (DENV) has not been developed yet. Among the different vaccination strategies available today, DNA vaccines are safe and practical, but currently induce relatively weak immune responses in humans. In order to improve immunogenicity, antigens may be targeted to dendritic cells (DCs), the main antigen presenting cells and orchestrators of the adaptive immune response, inducing T and B cell activation. It was previously shown that a DNA vaccine encoding a fusion protein comprised of an antigen and a single-chain Fv antibody (scFv) specific for the DC endocytic receptor DEC205 induced strong immune responses to the targeted antigen. In this work, we evaluate this strategy to improve the immunogenicity of dengue virus (DENV) proteins. Plasmids encoding the scFv a DEC205, or an isotype control (scFv ISO), fused to the DENV2 envelope protein domain III (EDIII) were generated, and EDIII specific immune responses were evaluated in immunized mice. BALB/c mice were intramuscularly (i. m.) immunized three times with plasmid DNAs encoding either scDEC-EDIII or scISO-EDIII followed by electroporation. Analyses of the antibody responses indicated that EDIII fusion with scFv targeting the DEC205 receptor significantly enhanced serum anti-EDIII IgG titers that inhibited DENV2 infection. Similarly, mice immunized with the scDEC-EDIII plasmid developed a robust CD4(+) T cell response to the targeted antigen, allowing the identification of two linear epitopes recognized by the BALB/c haplotype. Taken together, these results indicate that targeting DENV2 EDIII protein to DCs using a DNA vaccine encoding the scFv a DEC205 improves both antibody and CD4(+) T cell responses. This strategy opens perspectives for the use of DNA vaccines that encode antigens targeted to DCs as a strategy to increase immunogenicity. (AU)

• FAPESP's process: 16/04477-4 - Dendritic cell targeting with a DNA vaccine encoding the domain iii of the protein e of dengue virus
• Grantee: Arthur Baruel Zaneti
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/11442-4 - Study of protective mechanisms induced by vaccination of mice with fusion antibodies that target the dengue virus proteins to dendritic cells
• Grantee: Silvia Beatriz Boscardin
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50631-0 - Imaging and improvement of immune protection against malaria parasites
• Grantee: Silvia Beatriz Boscardin
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/17595-0 - New vaccine research based on recombinant proteins of dengue virus
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/16565-2 - Evaluation of humoral and cellular immune responses induced by targeting the domain III of the dengue virus envelope protein to the DEC205+ dendritic cell subpopulation.
• Grantee: Bianca da Silva Almeida
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/15061-8 - In vivo targetting of HIV- CD4+ t cell epitopes to dendritic cells
• Grantee: Daniela Santoro Rosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/18874-2 - Mechanism of Generation of humoral immune response induced by targeting of MSP1(19)-PADRE antigen to two different subsets of dendritic cells via DEC205 and DCIR2 receptors
• Grantee: Fernando Bandeira Sulczewski
• Support Opportunities: Scholarships in Brazil - Master