title: Dendritic Cell Targeting Effectively Boosts T Cell Responses Elicited by an HIV Multiepitope DNA Vaccine.
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 αDEC205 (αDECHIVBr8), 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 αDECHIVBr8 presented higher CD4+and CD8+T cell responses when compared to mice that received the DNA vaccine (pVAXHIVBr8). In addition, pVAXHIVBr8 priming followed by αDECHIVBr8 boosting induced higher polyfunctional proliferative and cytokine-producing T cell responses to HIV-1 peptides than homologous DNA immunization or heterologous αDEC 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.
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil.
authors.forename: Juliana de Souza
authors.initials: JS
authors.lastname: Apostólico
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM) , São Paulo , Brazil.
authors.forename: Victória Alves Santos
authors.initials: VA
authors.lastname: Lunardelli
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.
authors.forename: Marcio Massao
authors.initials: MM
authors.lastname: Yamamoto
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil.
authors.forename: Higo Fernando Santos
authors.initials: HF
authors.lastname: Souza
authors.affiliation: Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil; Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine, São Paulo, Brazil; Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
authors.affiliation: Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Silvia Beatriz
authors.initials: SB
authors.lastname: Boscardin
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil.
authors.forename: Daniela Santoro
authors.initials: DS
authors.lastname: Rosa
keywords: CD4+ T cell; HIV; dendritic cells; monoclonal antibody; multiepitope vaccine