评估表达环子孢子蛋白和ME-TRAP的ChAd63-MVA载体疫苗对未感染疟疾个体的受控人类疟疾感染的疗效。

Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.

作者信息

Hodgson Susanne H, Ewer Katie J, Bliss Carly M, Edwards Nick J, Rampling Thomas, Anagnostou Nicholas A, de Barra Eoghan, Havelock Tom, Bowyer Georgina, Poulton Ian D, de Cassan Simone, Longley Rhea, Illingworth Joseph J, Douglas Alexander D, Mange Pooja B, Collins Katharine A, Roberts Rachel, Gerry Stephen, Berrie Eleanor, Moyle Sarah, Colloca Stefano, Cortese Riccardo, Sinden Robert E, Gilbert Sarah C, Bejon Philip, Lawrie Alison M, Nicosia Alfredo, Faust Saul N, Hill Adrian V S

机构信息

Jenner Institute.

Jenner Institute Royal College of Surgeons in Ireland, Dublin, Ireland.

出版信息

J Infect Dis. 2015 Apr 1;211(7):1076-86. doi: 10.1093/infdis/jiu579. Epub 2014 Oct 21.

DOI:10.1093/infdis/jiu579

PMID:25336730

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4354983/

Abstract

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.

摘要

背景

环子孢子蛋白（CS）是RTS,S（迄今为止最先进的疟疾疫苗）的抗原靶点。用病毒载体猿猴腺病毒63（ChAd63）-改良安卡拉痘苗病毒（MVA）进行异源初免-加强免疫是人类T细胞的最有效诱导方式，在表达前红细胞期抗原插入物多表位-血小板反应蛋白相关黏附蛋白（ME-TRAP）时显示出显著疗效。我们推测，含CS的ChAd63-MVA可能产生显著的临床保护效力。

方法

我们开展了一项开放标签、2个地点、部分随机的恶性疟原虫子孢子控制的人体疟疾感染（CHMI）研究，以比较ChAd63-MVA CS与ChAd63-MVA ME-TRAP的临床疗效。

结果

15名接受ChAd63-MVA CS的疫苗接种者中有1名（7%）以及15名接受ChAd63-MVA ME-TRAP的疫苗接种者中有2名（13%）在CHMI后实现了无菌保护。15名接受ChAd63-MVA CS的疫苗接种者中有3名（20%）以及15名接受ChAd63-MVA ME-TRAP的疫苗接种者中有5名（33%）与未接种疫苗的对照组相比，显示出治疗时间延迟。在定量聚合酶链反应分析中，估计ChAd63-MVA CS可使肝脏寄生虫负荷降低69%-79%，而ChAd63-MVA ME-TRAP为79%-84%。