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.
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DOI：
10.3389/fimmu.2017.00101
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发表时间：
2017
影响因子：
7.3
通讯作者：
Rosa DS
中科院分区：
文献类型：
--
作者：
Apostólico JS;Lunardelli VA;Yamamoto MM;Souza HF;Cunha-Neto E;Boscardin SB;Rosa DS
尽管在过去的几十年里做出了几次努力，但仍然没有有效的艾滋病毒-1疫苗。人们对不同的方法进行了评估，如重组蛋白、病毒载体、DNA疫苗，以及最近的树突状细胞(DC)靶向。这一策略是基于DC的特征，将它们置于诱导免疫的中心。靶向是通过使用针对DC表面受体的嵌合单抗融合到目标抗原来实现的。在这项工作中，我们通过在α激动剂Poly(I：C)的存在下，将多表位免疫原与TLR3DEC205重链(αDECHIVBr8)融合，将8个混合的HIV来源的CD4+T细胞表位(HIVBr8)靶向DEC205+DC。此外，我们使用同源或异源Prime-Boost方案测试了编码相同表位的DNA疫苗。我们的结果显示，与接受α疫苗(PVAXHIVBr8)免疫的小鼠相比，接种pVAXHIVBr8的小鼠表现出更高的CD4+和CD8+T细胞应答。此外，pVAXHIVBr8免疫后的αDECHIVBr8 Boost诱导的多功能增殖和产生细胞因子的T细胞对α-1多肽的应答高于同种或异种DEC Prime/DNABoost。基于这些结果，我们得出结论，与单独的DNA免疫相比，针对DC的同源Prime-Boost和异源增强免疫策略在提高HIV特异性细胞免疫应答方面是有效的。此外，我们的结果表明，抗原靶向DC是一种有效的策略，以提高对多表位免疫原的免疫力，特别是在DNA疫苗的背景下。
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.