Combined skin and muscle vaccination differentially impact the quality of effector T cell functions: the CUTHIVAC-001 randomized trial.
Combined skin and muscle vaccination differentially impact the quality of effector T cell functions: the CUTHIVAC-001 randomized trial.
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DOI：
10.1038/s41598-017-13331-1
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发表时间：
2017-10-12
影响因子：
4.6
通讯作者：
Shattock RJ
中科院分区：
文献类型：
--
作者：
Haidari G;Cope A;Miller A;Venables S;Yan C;Ridgers H;Reijonen K;Hannaman D;Spentzou A;Hayes P;Bouliotis G;Vogt A;Joseph S;Combadiere B;McCormack S;Shattock RJ
通过经皮（TC），皮内（ID）和肌肉内（IM）注射对不同组织的靶向有可能在此阶段对DNA疫苗的免疫响应来定制IN IN IN HIV-1阴性志愿者。 DNA疫苗的模式影响了细胞免疫调查的质量。给药。 IM+EP给出的诱导病毒特异性CD4+和CD8+细胞介导的免疫呼吸促进了强烈的IFN-γ反应和潜在的病毒抑制。没有EP的ID+IM产生了类似的响应模式，但通过对比度TC+IM（没有EP）将反应转移到与粘膜和表皮保护相关的更为th-17的主导地位结果为抵抗各种复杂和多样化的传染病和癌症所需的细胞免疫学的不同形状提供了新的观点。
Targeting of different tissues via transcutaneous (TC), intradermal (ID) and intramuscular (IM) injection has the potential to tailor the immune response to DNA vaccination. In this Phase I randomised controlled clinical trial in HIV-1 negative volunteers we investigate whether the site and mode of DNA vaccination influences the quality of the cellular immune responses. We adopted a strategy of concurrent immunization combining IM injection with either ID or TC administration. As a third arm we assessed the response to IM injection administered with electroporation (EP). The DNA plasmid encoded a MultiHIV B clade fusion protein designed to induce cellular immunity. The vaccine and regimens were well tolerated. We observed differential shaping of vaccine induced virus-specific CD4 + and CD8 + cell-mediated immune responses. DNA given by IM + EP promoted strong IFN-γ responses and potent viral inhibition. ID + IM without EP resulted in a similar pattern of response but of lower magnitude. By contrast TC + IM (without EP) shifted responses towards a more Th-17 dominated phenotype, associated with mucosal and epidermal protection. Whilst preliminary, these results offer new perspectives for differential shaping of desired cellular immunity required to fight the wide range of complex and diverse infectious diseases and cancers.
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