Data from: 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

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.研究背景：新型结核病疫苗需在包括人类免疫缺陷病毒（HIV, Human Immunodeficiency Virus）感染者在内的各类人群中具备安全性、免疫原性与有效性。本项Ⅱ期多中心双盲安慰剂对照临床试验，针对以佐剂IC31配制的Ag85B-ESAT-6融合蛋白（H1）组成的新型H1/IC31疫苗，在HIV感染成人群体中评估其安全性与免疫原性。 研究方法：纳入CD4+T淋巴细胞（CD4+ T cell）计数＞350/mm³且无活动性结核病证据的HIV感染成人受试者，随访至第182天。按5:1的比例随机分配受试者接受H1/IC31疫苗或安慰剂。疫苗分别于第0天和第56天经肌肉注射给药。安全性评估基于病史采集、临床检查以及血液与尿液检测。免疫原性通过短期全血细胞内细胞因子染色试验进行测定。 研究结果：48名随机入组受试者中，47名完成了两剂次疫苗接种。总计报告459例轻中度不良事件与2例重度不良事件。2名疫苗接种者共发生3例严重不良事件，经判定与研究受试产品无关。与安慰剂组相比，H1/IC31组受试者更易出现局部注射部位反应（65.0% vs. 12.5%，p = 0.015）。征集性全身不良事件与非征集性不良事件的发生率在两组间无显著差异。两组受试者的基线CD4+T淋巴细胞计数与HIV病毒载量无显著差异，且随时间推移保持稳定。H1/IC31疫苗可诱导持久的Th1型免疫应答（Th1 immune response），以共表达肿瘤坏死因子-α（TNF-α, Tumor Necrosis Factor-α）与白细胞介素-2（IL-2, Interleukin-2）的CD4+T细胞为主，同时亦可诱导表达干扰素-γ（IFN-γ, Interferon-γ）、TNF-α与IL-2的多功能性CD4+T细胞。 研究结论：H1/IC31疫苗在CD4+淋巴细胞计数＞350个/mm³的HIV感染成人中耐受性良好且安全性可靠。该疫苗对受试者的CD4+T淋巴细胞计数或HIV-1病毒载量无影响。H1/IC31可诱导特异性且持久的Th1型免疫应答。