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

Autor(es)

Apostolico, Juliana de Souza ; Santos Lunardelli, Victoria Alves ; Yamamoto, Marcio Massao ; Santos Souza, Higo Fernando ; Cunha-Neto, Edecio ; Boscardin, Silvia Beatriz ; Rosa, Daniela Santoro

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 8, FEB 7 2017.
• Citações Web of Science: 10

Resumo

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)

• Processo FAPESP: 14/15061-8 - Direcionamento in vivo de epitopos de linfócitos TCD4+ do HIV-1 para células dendríticas
• Beneficiário: Daniela Santoro Rosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/11442-4 - Estudo dos mecanismos protetores induzidos pela vacinação de camundongos com anticorpos de fusão capazes de direcionar proteínas do vírus da dengue para células dendríticas
• Beneficiário: Silvia Beatriz Boscardin
• Modalidade de apoio: Auxílio à Pesquisa - Regular