Kimani Domtila, Jagne Ya Jankey, Cox Momodou, Kimani Eva, Bliss Carly M, Gitau Evelyn, Ogwang Caroline, Afolabi Muhammed O, Bowyer Georgina, Collins Katharine A, Edwards Nick, Hodgson Susanne H, Duncan Christopher J A, Spencer Alexandra J, Knight Miguel G, Drammeh Abdoulie, Anagnostou Nicholas A, Berrie Eleanor, Moyle Sarah, Gilbert Sarah C, Soipei Peninah, Okebe Joseph, Colloca Stefano, Cortese Riccardo, Viebig Nicola K, Roberts Rachel, Lawrie Alison M, Nicosia Alfredo, Imoukhuede Egeruan B, Bejon Philip, Chilengi Roma, Bojang Kalifa, Flanagan Katie L, Hill Adrian V S, Urban Britta C, Ewer Katie J
Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.
Medical Research Council Unit, Fajara, The Gambia.
Mol Ther. 2014 Nov;22(11):1992-2003. doi: 10.1038/mt.2014.109. Epub 2014 Jun 16.
To induce a deployable level of efficacy, a successful malaria vaccine would likely benefit from both potent cellular and humoral immunity. These requirements are met by a heterologous prime-boost immunization strategy employing a chimpanzee adenovirus vector followed by modified vaccinia Ankara (MVA), both encoding the pre-erythrocytic malaria antigen ME-thrombospondin-related adhesive protein (TRAP), with high immunogenicity and significant efficacy in UK adults. We undertook two phase 1b open-label studies in adults in Kenya and The Gambia in areas of similar seasonal malaria transmission dynamics and have previously reported safety and basic immunogenicity data. We now report flow cytometry and additional interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) data characterizing pre-existing and induced cellular immunity as well as anti-TRAP IgG responses. T-cell responses induced by vaccination averaged 1,254 spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) across both trials and flow cytometry revealed cytokine production from both CD4(+) and CD8(+) T cells with the frequency of CD8(+) IFN-γ-secreting monofunctional T cells (previously shown to associate with vaccine efficacy) particularly high in Kenyan adults. Immunization with ChAd63 and MVA ME-TRAP induced strong cellular and humoral immune responses in adults living in two malaria-endemic regions of Africa. This prime-boost approach targeting the pre-erythrocytic stage of the malaria life-cycle is now being assessed for efficacy in a target population.
为诱导出可达到有效水平的免疫效果，一种成功的疟疾疫苗可能需要强大的细胞免疫和体液免疫共同发挥作用。采用黑猩猩腺病毒载体，随后接种改良安卡拉痘苗病毒（MVA）的异源初免 - 加强免疫策略能够满足这些要求，这两种载体均编码红细胞前期疟疾抗原ME - 血小板反应蛋白相关黏附蛋白（TRAP），在英国成年人中具有高免疫原性和显著疗效。我们在肯尼亚和冈比亚的成年人中开展了两项1b期开放标签研究，这些地区的季节性疟疾传播动态相似，并且我们之前已经报告了安全性和基本免疫原性数据。我们现在报告流式细胞术以及额外的干扰素（IFN）-γ酶联免疫斑点（ELISPOT）数据，这些数据表征了预先存在的和诱导产生的细胞免疫以及抗TRAP IgG反应。在两项试验中，接种疫苗诱导的T细胞反应平均为每百万外周血单个核细胞（PBMC）中有1254个斑点形成细胞（SFC），流式细胞术显示CD4(+)和CD8(+) T细胞均产生细胞因子，其中分泌IFN-γ的CD8(+)单功能T细胞（先前已证明与疫苗疗效相关）的频率在肯尼亚成年人中特别高。用ChAd63和MVA ME - TRAP进行免疫接种，在生活在非洲两个疟疾流行地区的成年人中诱导了强烈的细胞免疫和体液免疫反应。这种针对疟疾生命周期红细胞前期阶段的初免 - 加强方法目前正在目标人群中评估其疗效。
