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

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

Author Apostolico, Juliana de Souza Autor UNIFESP Google Scholar
Santos Lunardelli, Victoria Alves Autor UNIFESP Google Scholar
Yamamoto, Marcio Massao Google Scholar
Santos Souza, Higo Fernando Google Scholar
Cunha-Neto, Edecio Google Scholar
Boscardin, Silvia Beatriz Google Scholar
Rosa, Daniela Santoro Autor UNIFESP Google Scholar
Abstract 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.
Keywords HIV
dendritic cells
multiepitope vaccine
CD4(+) T cell
monoclonal antibody
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Brazilian National Research Council (CNPq)/Institute for Investigation in Immunology
CNPq/FAPESP
CAPES
Grant number FAPESP: 2014/15061-8
FAPESP: 2013/11442-4
Date 2017
Published in Frontiers In Immunology. Lausanne, v. 8, p. -, 2017.
ISSN 1664-3224 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fimmu.2017.00101
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000393438100001
URI https://repositorio.unifesp.br/handle/11600/55117

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