H1/IC31®（一种含佐剂的结核亚单位疫苗）在CD4 +淋巴细胞计数大于350个细胞/mm3的HIV感染成人中的安全性和免疫原性：一项II期、多中心、双盲、随机、安慰剂对照试验。
Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.
作者信息
Reither Klaus, Katsoulis Lynn, Beattie Trevor, Gardiner Nicolene, Lenz Nicole, Said Khadija, Mfinanga Elirehema, Pohl Christian, Fielding Katherine L, Jeffery Hannah, Kagina Benjamin M, Hughes Elisabeth J, Scriba Thomas J, Hanekom Willem A, Hoff Søren T, Bang Peter, Kromann Ingrid, Daubenberger Claudia, Andersen Peter, Churchyard Gavin J
机构信息
Swiss Tropical and Public Health Institute, Basel, Switzerland; University Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, Tanzania.
Aurum Institute, Johannesburg, South Africa.
出版信息
PLoS One. 2014 Dec 9;9(12):e114602. doi: 10.1371/journal.pone.0114602. eCollection 2014.
BACKGROUND
Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults.
METHODS
HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay.
RESULTS
47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells.
CONCLUSION
H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response.
TRIAL REGISTRATION
Pan African Clinical Trials Registry (PACTR) PACTR201105000289276.
背景
新型结核病疫苗应在包括艾滋病毒感染者在内的各类人群中安全、具有免疫原性且有效。在这项II期多中心、双盲、安慰剂对照试验中，对新型H1/IC31疫苗（一种由Ag85B - ESAT - 6（H1）与佐剂IC31配制而成的融合蛋白）在艾滋病毒感染成人中的安全性和免疫原性进行了评估。
方法
纳入CD4 + T细胞计数>350/mm³且无活动性结核病证据的艾滋病毒感染成人，并随访至第182天。H1/IC31疫苗或安慰剂按5:1的比例随机分配。疫苗分别在第0天和第56天进行肌肉注射。安全性评估基于病史、临床检查以及血液和尿液检测。免疫原性通过短期全血细胞内细胞因子染色试验确定。
结果
48名随机分组的参与者中有47人完成了两次疫苗接种。总共报告了459例轻度或中度不良事件以及2例严重不良事件。两名疫苗接种者发生了3起严重不良事件，判定与研究产品无关。H1/IC31疫苗接种者的局部注射部位反应比安慰剂接种者更常见（65.0%对12.5%，p = 0.015）。各研究组中预期的全身性不良事件和非预期不良事件相似。各研究组的基线CD4 + T细胞计数和艾滋病毒病毒载量相似，且随时间保持稳定。H1/IC31疫苗诱导了持续的Th1免疫反应，主要是共表达TNF-α和IL-2的CD4 + T细胞，以及同时表达多功能IFN-γ、TNF-α和IL-2的CD4 + T细胞。
结论
H1/IC31在CD4 + 淋巴细胞计数大于350个细胞/mm³的艾滋病毒感染成人中耐受性良好且安全。该疫苗对CD4 + T细胞计数或艾滋病毒-1病毒载量没有影响。H1/IC31诱导了特异性且持久的Th1免疫反应。
试验注册
泛非临床试验注册中心（PACTR）PACTR201105000289276
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