Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
Vaccine. 2013 Feb 4;31(7):1026-33. doi: 10.1016/j.vaccine.2012.12.042. Epub 2012 Dec 21.
New vaccines to prevent tuberculosis are urgently needed. MVA85A is a novel viral vector TB vaccine candidate designed to boost BCG-induced immunity when delivered intradermally. To date, intramuscular delivery has not been evaluated. Skin and muscle have distinct anatomical and immunological properties which could impact upon vaccine-mediated cellular immunity.
We conducted a randomised phase I trial comparing the safety and immunogenicity of 1×10(8)pfu MVA85A delivered intramuscularly or intradermally to 24 healthy BCG-vaccinated adults.
Intramuscular and intradermal MVA85A were well tolerated. Intradermally-vaccinated subjects experienced significantly more local adverse events than intramuscularly-vaccinated subjects, with no difference in systemic adverse events. Both routes generated strong and sustained Ag85A-specific IFNγ T cell responses and induced multifunctional CD4+ T cells. The frequencies of CD4+ T cells expressing chemokine receptors CCR4, CCR6, CCR7 and CXCR3 induced by vaccination was similar between routes.
In this phase I trial the intramuscular delivery of MVA85A was well tolerated and induced strong, durable cellular immune responses in healthy BCG vaccinated adults, comparable to intradermal delivery. These findings are important for TB vaccine development and are of relevance to HIV, malaria, influenza and other intracellular pathogens for which T cell-inducing MVA-based vaccine platforms are being evaluated.
急需新的结核病疫苗。MVA85A 是一种新型病毒载体结核候选疫苗，旨在皮内接种时增强卡介苗诱导的免疫。迄今为止，尚未评估肌内递送。皮肤和肌肉具有不同的解剖学和免疫学特性，这可能会影响疫苗介导的细胞免疫。
我们进行了一项随机、I 期试验，比较了 1×10(8)pfu MVA85A 肌内或皮内接种 24 名健康卡介苗接种成年人的安全性和免疫原性。
肌内和皮内 MVA85A 均耐受良好。皮内接种组比肌内接种组发生更多的局部不良事件，但全身不良事件无差异。两种途径均产生强烈且持续的 Ag85A 特异性 IFNγ T 细胞反应，并诱导多功能 CD4+T 细胞。两种途径诱导的表达趋化因子受体 CCR4、CCR6、CCR7 和 CXCR3 的 CD4+T 细胞的频率相似。
在这项 I 期试验中，MVA85A 的肌内递送在健康的卡介苗接种成年人中耐受良好，并诱导强烈、持久的细胞免疫反应，与皮内递送相当。这些发现对结核病疫苗的开发很重要，并且与 HIV、疟疾、流感和其他正在评估基于 MVA 的 T 细胞诱导疫苗平台的细胞内病原体有关。
