van Doorn Eva, Pleguezuelos Olga, Liu Heng, Fernandez Ana, Bannister Robin, Stoloff Gregory, Oftung Fredrik, Norley Stephen, Huckriede Anke, Frijlink Henderik W, Hak Eelko
University of Groningen, Unit of PharmacoTherapy- Epidemiology & -Economics, Antonius Deusinglaan, 9713 AV, Groningen, The Netherlands.
SEEK, Central Point, 45 Beech Street, London, EC2Y 8AD, UK.
BMC Infect Dis. 2017 Apr 4;17(1):241. doi: 10.1186/s12879-017-2341-9.
Current influenza vaccines, based on antibodies against surface antigens, are unable to provide protection against newly emerging virus strains which differ from the vaccine strains. Therefore the population has to be re-vaccinated annually. It is thus important to develop vaccines which induce protective immunity to a broad spectrum of influenza viruses. This trial is designed to evaluate the immunogenicity and safety of FLU-v, a vaccine composed of four synthetic peptides with conserved epitopes from influenza A and B strains expected to elicit both cell mediated immunity (CMI) and humoral immunity providing protection against a broad spectrum of influenza viruses.
In a single-center, randomized, double-blind and placebo-controlled phase IIb trial, 222 healthy volunteers aged 18-60 years will be randomized (2:2:1:1) to receive two injections of a suspension of 500 μg FLU-v in saline (arm 1), one dose of emulsified 500 μg FLU-v in Montanide ISA-51 and water for injection (WFI) followed by one saline dose (arm 2), two saline doses (arm 3), or one dose of Montanide ISA-51 and WFI emulsion followed by one saline dose (arm 4). All injections will be given subcutaneously. Primary endpoints are safety and FLU-v induced CMI, evaluated by cytokine production by antigen specific T cell populations (flow-cytometry and ELISA). Secondary outcomes are measurements of antibody responses (ELISA and multiplex), whereas exploratory outcomes include clinical efficacy and additional CMI assays (ELISpot) to show cross-reactivity.
Broadly protective influenza vaccines able to provide protection against multiple strains of influenza are urgently needed. FLU-v is a promising vaccine which has shown to trigger the cell-mediated immune response. The dosages and formulations tested in this current trial are also estimated to induce antibody response. Therefore, both cellular and humoral immune responses will be evaluated.
EudraCT number 2015-001932-38 ; retrospectively registered clinicaltrials.gov NCT02962908 (November 7th 2016).
目前基于针对表面抗原的抗体的流感疫苗，无法对与疫苗毒株不同的新出现病毒株提供保护。因此，人群必须每年重新接种疫苗。所以，研发能诱导对广谱流感病毒产生保护性免疫的疫苗很重要。本试验旨在评估FLU-v疫苗的免疫原性和安全性，该疫苗由四种合成肽组成，这些合成肽具有来自甲型和乙型流感毒株的保守表位，预期能引发细胞介导免疫（CMI）和体液免疫，从而提供针对广谱流感病毒的保护。
在一项单中心、随机、双盲和安慰剂对照的IIb期试验中，222名年龄在18至60岁的健康志愿者将被随机分组（2:2:1:1），分别接受两次500μg FLU-v盐水悬液注射（第1组）、一剂500μg FLU-v与Montanide ISA-51和注射用水（WFI）乳化后的制剂，随后再注射一剂盐水（第2组）、两剂盐水（第3组）或一剂Montanide ISA-51和WFI乳剂，随后再注射一剂盐水（第4组）。所有注射均采用皮下注射。主要终点是安全性和FLU-v诱导的CMI，通过抗原特异性T细胞群体产生的细胞因子（流式细胞术和酶联免疫吸附测定）进行评估。次要结果是抗体反应的测量（酶联免疫吸附测定和多重检测），而探索性结果包括临床疗效和额外的CMI检测（酶联免疫斑点法）以显示交叉反应性。
迫切需要能对多种流感毒株提供保护的广谱保护性流感疫苗。FLU-v是一种有前景的疫苗，已显示能触发细胞介导的免疫反应。本次试验中测试的剂量和制剂预计也能诱导抗体反应。因此，将对细胞免疫和体液免疫反应进行评估。
欧洲临床试验数据库编号2015-001932-38；回顾性注册于美国国立医学图书馆临床试验数据库NCT02962908（2016年11月7日）。
