Human adenovirus 5-vectored Plasmodium falciparum NMRC-M3V-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection.
Human adenovirus 5-vectored Plasmodium falciparum NMRC-M3V-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection.
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DOI：
10.4161/hv.24941
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发表时间：
2013-10
影响因子：
4.8
通讯作者：
Richie TL
中科院分区：
文献类型：
--
作者：
Tamminga C;Sedegah M;Maiolatesi S;Fedders C;Reyes S;Reyes A;Vasquez C;Alcorta Y;Chuang I;Spring M;Kavanaugh M;Ganeshan H;Huang J;Belmonte M;Abot E;Belmonte A;Banania J;Farooq F;Murphy J;Komisar J;Richie NO;Bennett J;Limbach K;Patterson NB;Bruder JT;Shi M;Miller E;Dutta S;Diggs C;Soisson LA;Hollingdale MR;Epstein JE;Richie TL
背景资料：在先前的研究中，表达恶性疟原虫环子孢子蛋白（CSP）和顶端膜抗原-1（AMA 1）的DNA初免/腺病毒加强疫苗（DNA/Ad）（NMRC-M3 V-D/Ad-PfCA疫苗）诱导了27%的针对受控人疟疾感染（CHMI）的保护。为了研究DNA引发的贡献，我们在1期临床试验中测试了单独的腺病毒疫苗（NMRC-M3 V-Ad-PfCA）的功效。方法/主要发现：该方案是分别编码CSP和AMA 1的两种非复制型人血清5型腺载体的单次肌内注射。在给药前将每种构建体的1 × 1010个颗粒单位合并。该方案安全且耐受性良好。四周后，18名研究受试者通过蚊子叮咬接受了恶性疟原虫CHMI。没有一个得到充分保护，但一个显示寄生虫血症延迟发作。抗体应答较低，几何平均CSP ELISA滴度为381（范围50-1626），AMA 1 ELISA滴度为4.95 µg/mL（范围0.2-38）。对重叠肽的体外IFN-γ ELISpot应答的总和是稳健的，CSP的几何平均斑点形成细胞/百万外周血单核细胞[sfc/m]为273（范围38-2550），AMA 1的几何平均斑点形成细胞/百万外周血单核细胞[sfc/m]为1303（范围435-4594）。通过流式细胞术检测，CD 4+和CD 8 + T细胞对CSP的IFN-γ应答分别为25%和56%，对AMA 1的应答分别为94%和100%。重要性：与DNA/Ad相反，单独的Ad尽管诱导广泛的细胞介导的免疫力，但不能保护CHMI，这表明DNA引发是腺病毒载体疫苗保护所必需的。ClinicalTrials.gov标识符：NCT 00392015。
Background: In a prior study, a DNA prime / adenovirus boost vaccine (DNA/Ad) expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) (NMRC-M3V-D/Ad-PfCA Vaccine) induced 27% protection against controlled human malaria infection (CHMI). To investigate the contribution of DNA priming, we tested the efficacy of adenovirus vaccine alone (NMRC-M3V-Ad-PfCA ) in a Phase 1 clinical trial. Methodology/Principal Findings: The regimen was a single intramuscular injection with two non-replicating human serotype 5 adenovectors encoding CSP and AMA1, respectively. One x 1010 particle units of each construct were combined prior to administration. The regimen was safe and well-tolerated. Four weeks later, 18 study subjects received P. falciparum CHMI administered by mosquito bite. None were fully protected although one showed delayed onset of parasitemia. Antibody responses were low, with geometric mean CSP ELISA titer of 381 (range < 50–1626) and AMA1 ELISA of 4.95 µg/mL (range 0.2–38). Summed ex vivo IFN-γ ELISpot responses to overlapping peptides were robust, with geometric mean spot forming cells/million peripheral blood mononuclear cells [sfc/m] for CSP of 273 (range 38–2550) and for AMA1 of 1303 (range 435–4594). CD4+ and CD8+ T cell IFN-γ responses to CSP were positive by flow cytometry in 25% and 56% of the research subjects, respectively, and to AMA1 in 94% and 100%, respectively. Significance: In contrast to DNA/Ad, Ad alone did not protect against CHMI despite inducing broad, cell-mediated immunity, indicating that DNA priming is required for protection by the adenovirus-vectored vaccine. ClinicalTrials.gov Identifier: NCT00392015.
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影响因子：
5.5
作者：
Le, TP;Coonan, KM;Hoffman, SL
通讯作者：
Hoffman, SL
影响因子：
30.3
作者：
Butler NS;Schmidt NW;Vaughan AM;Aly AS;Kappe SH;Harty JT
通讯作者：
Harty JT
影响因子：
4.4
作者：
Holst, Peter Johannes;Orskov, Cathrine;Christensen, Jan Pravsgaard
通讯作者：
Christensen, Jan Pravsgaard
DOI：
10.1073/pnas.91.21.9866
发表时间：
1994-10-11
影响因子：
11.1
作者：
SEDEGAH, M;HEDSTROM, R;HOFFMAN, SL
通讯作者：
HOFFMAN, SL
影响因子：
4.2
作者：
Epstein, JE;Gorak, EJ;Hoffman, SL
通讯作者：
Hoffman, SL