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

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dc.citation.volume8
dc.contributor.authorApostolico, Juliana de Souza [UNIFESP]
dc.contributor.authorSantos Lunardelli, Victoria Alves [UNIFESP]
dc.contributor.authorYamamoto, Marcio Massao
dc.contributor.authorSantos Souza, Higo Fernando
dc.contributor.authorCunha-Neto, Edecio
dc.contributor.authorBoscardin, Silvia Beatriz
dc.contributor.authorRosa, Daniela Santoro [UNIFESP]
dc.coverageLausanne
dc.date.accessioned2020-07-17T14:02:59Z
dc.date.available2020-07-17T14:02:59Z
dc.date.issued2017
dc.description.abstractDespite 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.en
dc.description.affiliationFed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationINCT, Inst Invest Immunol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Sch Med, Lab Clin Immunol & Allergy LIM60, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Sch Med, Heart Inst InCor, Immunol Lab, Sao Paulo, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipBrazilian National Research Council (CNPq)/Institute for Investigation in Immunology
dc.description.sponsorshipCNPq/FAPESP
dc.description.sponsorshipCAPES
dc.description.sponsorshipIDFAPESP: 2014/15061-8
dc.description.sponsorshipIDFAPESP: 2013/11442-4
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fimmu.2017.00101
dc.identifier.citationFrontiers In Immunology. Lausanne, v. 8, p. -, 2017.
dc.identifier.doi10.3389/fimmu.2017.00101
dc.identifier.fileWOS000393438100001.pdf
dc.identifier.issn1664-3224
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55117
dc.identifier.wosWOS:000393438100001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Immunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHIVen
dc.subjectdendritic cellsen
dc.subjectmultiepitope vaccineen
dc.subjectCD4(+) T cellen
dc.subjectmonoclonal antibodyen
dc.titleDendritic Cell Targeting Effectively Boosts T Cell Responses Elicited by an HIV Multiepitope DNA Vaccineen
dc.typeinfo:eu-repo/semantics/article
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