Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.
Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.
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评估表达外孢子虫蛋白和ME捕获的CHAD63-MVA矢量疫苗对疟疾个体中受控的人类疟疾感染的疗效。
DOI：
10.1093/infdis/jiu579
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发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Hill AV
中科院分区：
文献类型：
--
作者：
Hodgson SH;Ewer KJ;Bliss CM;Edwards NJ;Rampling T;Anagnostou NA;de Barra E;Havelock T;Bowyer G;Poulton ID;de Cassan S;Longley R;Illingworth JJ;Douglas AD;Mange PB;Collins KA;Roberts R;Gerry S;Berrie E;Moyle S;Colloca S;Cortese R;Sinden RE;Gilbert SC;Bejon P;Lawrie AM;Nicosia A;Faust SN;Hill AV
环子孢子蛋白（CS）是目前最先进的疟疾疫苗RTS，S的抗原靶点。用病毒载体猿猴腺病毒63（ChAd 63）修饰的安卡拉牛痘病毒（MVA）进行的异源性初免-加强是人类中最有效的T细胞诱导剂，当表达红细胞前抗原插入多表位-血小板反应蛋白相关粘附蛋白（ME-TRAP）时显示出显著的功效。我们假设含有CS的ChAd 63-MVA可能导致显著的临床保护功效。方法：我们进行了一项开放标签、双中心、部分随机的恶性疟原虫子孢子控制的人类疟疾感染（CHMI）研究，以比较ChAd 63-MVA CS与ChAd 63-MVA ME-TRAP的临床疗效。 结果：CHMI后，15名接受ChAd 63-MVA CS的疫苗接种者中有1名（7%）和15名接受ChAd 63-MVA ME-TRAP的疫苗接种者中有2名（13%）获得了无菌保护。 与未接种疫苗的对照组相比，接受ChAd 63-MVA CS的15名疫苗接种者中有3名（20%）和接受ChAd 63-MVA ME-TRAP的15名疫苗接种者中有5名（33%）表现出治疗时间延迟。在定量聚合酶链反应分析中，ChAd 63-MVA CS估计可使肝脏寄生虫负荷降低69%-79%，而ChAd 63-MVA ME-TRAP为79%-84%。结论：ChAd 63-MVA CS确实减少了肝脏寄生虫的负担，但是ChAd 63-MVA ME-TRAP仍然是载体肝脏阶段疫苗最有希望的抗原插入物。 寄生虫动力学的详细分析可能允许检测可能影响未来疫苗开发的疫苗功效的较小但具有生物学重要性的差异。临床试验注册。NCT 01623557。
Background. Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope–thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy. Methods. We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. Results. One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%–79%, compared with 79%–84% for ChAd63-MVA ME-TRAP. Conclusions. ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development. Clinical Trials Registration. NCT01623557.
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影响因子：
6.4
作者：
Bejon, P;Andrews, L;Hill, AVS
通讯作者：
Hill, AVS
影响因子：
11.8
作者：
Bejon, P;Peshu, N;Marsh, K
通讯作者：
Marsh, K
影响因子：
56.9
作者：
HOFFMAN, SL;ISENBARGER, D;BALLOU, WR
通讯作者：
BALLOU, WR
影响因子：
158.5
作者：
Mian-McCarthy, Sara;Agnandji, Selidji Todagbe;Vansadia, Preeti
通讯作者：
Vansadia, Preeti
DOI：
10.4161/hv.6.1.10116
发表时间：
2010-01-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Hill, Adrian V. S.;Reyes-Sandoval, Arturo;Draper, Simon J.
通讯作者：
Draper, Simon J.