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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Dendritic Cell Targeting Effectively Boosts T Cell Responses Elicited by an HIV Multiepitope DNA Vaccine

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Apostolico, Juliana de Souza ; Santos Lunardelli, Victoria Alves ; Yamamoto, Marcio Massao ; Santos Souza, Higo Fernando ; Cunha-Neto, Edecio ; Boscardin, Silvia Beatriz ; Rosa, Daniela Santoro
Total Authors: 7
Document type: Journal article
Source: FRONTIERS IN IMMUNOLOGY; v. 8, FEB 7 2017.
Web of Science Citations: 10

Despite several efforts in the last decades, an efficacious HIV-1 vaccine is still not available. Different approaches have been evaluated, such as recombinant proteins, viral vectors, DNA vaccines, and, most recently, dendritic cell (DC) targeting. This strategy is based on DC features that place them as central for induction of immunity. Targeting is accomplished by the use of chimeric monoclonal antibodies directed to DC surface receptors fused to the antigen of interest. In this work, we targeted eight promiscuous HIV-derived CD4(+) T cell epitopes (HIVBr8) to the DEC205(+) DCs by fusing the multiepitope immunogen to the heavy chain of alpha DEC205 (alpha DECHIVBr8), in the presence of the TLR3 agonist poly (I: C). In addition, we tested a DNA vaccine encoding the same epitopes using homologous or heterologous prime-boost regimens. Our results showed that mice immunized with alpha DECHIVBr8 presented higher CD4(+) and CD8(+) T cell responses when compared to mice that received the DNA vaccine (pVAXHIVBr8). In addition, pVAXHIVBr8 priming followed by alpha DECHIVBr8 boosting induced higher polyfunctional proliferative and cytokine-producing T cell responses to HIV-1 peptides than homologous DNA immunization or heterologous alpha DEC prime/DNA boost. Based on these results, we conclude that homologous prime-boost and heterologous boosting immunization strategies targeting CD4(+) epitopes to DCs are effective to improve HIV-specific cellular immune responses when compared to standalone DNA immunization. Moreover, our results indicate that antigen targeting to DC is an efficient strategy to boost immunity against a multiepitope immunogen, especially in the context of DNA vaccination. (AU)

FAPESP's process: 14/15061-8 - In vivo targetting of HIV- CD4+ t cell epitopes to dendritic cells
Grantee:Daniela Santoro Rosa
Support type: Regular Research Grants
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 type: Regular Research Grants