Brookes Roger H, Hill Philip C, Owiafe Patrick K, Ibanga Hannah B, Jeffries David J, Donkor Simon A, Fletcher Helen A, Hammond Abdulrahman S, Lienhardt Christian, Adegbola Richard A, McShane Helen, Hill Adrian V S
Bacterial Diseases Programme, Tuberculosis Division, Medical Research Council Laboratories, Fajara, Banjul, The Gambia.
PLoS One. 2008 Aug 13;3(8):e2921. doi: 10.1371/journal.pone.0002921.
Vaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicity of this new vaccine in West African volunteers.
We vaccinated 21 healthy adult male subjects (11 BCG scar negative and 10 BCG scar positive) with MVA85A after screening for evidence of prior exposure to mycobacteria. We monitored them over six months, observing for clinical, haematological and biochemical adverse events, together with assessment of the vaccine induced cellular immune response using ELISPOT and flow cytometry. MVA85A was well tolerated with no significant adverse events. Mild local and systemic adverse events were consistent with previous UK trials. Marked immunogenicity was found whether individuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-naïve Gambians than previously studied BCG-naïve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis.
These data on the safety and immunogenicity of MVA85A in West Africa support its accelerated development as a promising booster vaccine for tuberculosis.
ClinicalTrials.gov NCT00423839.
用表达结核分枝杆菌抗原85A的重组改良安卡拉痘苗（MVA85A）对英国志愿者进行疫苗接种，可诱导高水平的细胞免疫反应。我们评估了这种新型疫苗在西非志愿者中的安全性和免疫原性。
在筛选有既往接触分枝杆菌证据后，我们用MVA85A对21名健康成年男性受试者（11名卡介苗接种疤痕阴性和10名卡介苗接种疤痕阳性）进行了疫苗接种。我们对他们进行了六个月的监测，观察临床、血液学和生化不良事件，并使用酶联免疫斑点法（ELISPOT）和流式细胞术评估疫苗诱导的细胞免疫反应。MVA85A耐受性良好，无显著不良事件。轻度局部和全身不良事件与英国先前的试验一致。无论个体是否有既往卡介苗接种疤痕，均发现有明显的免疫原性。卡介苗接种疤痕阳性者的免疫原性未增强，在明显未接种卡介苗的冈比亚人中诱导的T细胞反应比先前研究的未接种卡介苗的英国疫苗接种者维持得更好。虽然反应主要归因于CD4 + T细胞，但我们也在HLA B - 35且有足够血液用于更详细免疫分析的受试者中鉴定出了抗原特异性CD8 + T细胞反应。
这些关于MVA85A在西非的安全性和免疫原性的数据支持其作为一种有前景的结核病加强疫苗加速研发。
ClinicalTrials.gov NCT00423839。
