Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study.
Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study.
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DOI：
10.3389/fimmu.2020.586124
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发表时间：
2020
影响因子：
7.3
通讯作者：
Combadiere B
中科院分区：
文献类型：
--
作者：
Sanchez J;Gonçalves E;Llano A;Gonzáles P;Fernández-Maldonado M;Vogt A;Soria A;Perez S;Cedeño S;Fernández MA;Nourikyan J;de Bernard S;Ganoza C;Pedruzzi E;Bonduelle O;Mothe B;Gòmez CE;Esteban M;Garcia F;Lama JR;Brander C;Combadiere B
我们以前的工作已经证明了经皮免疫在靶向朗格汉斯细胞和优先诱导CD8T细胞反应方面的好处。在这项包括20名未感染HIV的志愿者的随机Ib期临床试验中，我们比较了表达HIV-B抗原的MVA重组疫苗(MVA-B)经皮和肌肉注射的安全性和免疫原性。我们假设天然免疫和获得性免疫的质量根据免疫途径的不同而不同，并探索了载体疫苗诱导的免疫反应的质量。我们还调查了早期血液转录组和血清细胞因子水平，以确定与适应性免疫的强度和质量相关的先天事件。我们证明MVA-B疫苗在这两种途径上都是安全的，但先天免疫和获得性免疫的质量和强度都有显著差异。经皮接种可在没有抗体的情况下促进CD8反应，并对基因表达略有影响，主要涉及与代谢途径相关的基因。另一方面，肌肉接种推动了涉及IL-6和干扰素信号通路的基因表达的强劲变化，主要是那些与体液反应相关的基因，以及一些水平的CD8反应。因此，疫苗投放途径扰乱了影响适应性免疫质量的早期先天反应。，标识符PER-073-13。
Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses. In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-B antigen (MVA-B) by transcutaneous and intramuscular routes. We hypothesized that the quality of innate and adaptive immunity differs according to the route of immunization and explored the quality of the vector vaccine-induced immune responses. We also investigated the early blood transcriptome and serum cytokine levels to identify innate events correlated with the strength and quality of adaptive immunity. We demonstrate that MVA-B vaccine is safe by both routes, but that the quality and intensity of both innate and adaptive immunity differ significantly. Transcutaneous vaccination promoted CD8 responses in the absence of antibodies and slightly affected gene expression, involving mainly genes associated with metabolic pathways. Intramuscular vaccination, on the other hand, drove robust changes in the expression of genes involved in IL-6 and interferon signalling pathways, mainly those associated with humoral responses, and also some levels of CD8 response. Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity. , identifier PER-073-13.