Phase 1 study in malaria naïve adults of BSAM2/Alhydrogel®+CPG 7909, a blood stage vaccine against P. falciparum malaria.
Phase 1 study in malaria naïve adults of BSAM2/Alhydrogel®+CPG 7909, a blood stage vaccine against P. falciparum malaria.
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DOI：
10.1371/journal.pone.0046094
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Durbin AP
中科院分区：
文献类型：
--
作者：
Ellis RD;Wu Y;Martin LB;Shaffer D;Miura K;Aebig J;Orcutt A;Rausch K;Zhu D;Mogensen A;Fay MP;Narum DL;Long C;Miller L;Durbin AP
在未感染疟疾的成人中进行了1期剂量递增研究，以评估血液阶段疟疾疫苗BSAM 2/Alhydrogel®+ CPG 7909的安全性、反应原性和免疫原性。BSAM 2是重组AMA 1和MSP 142的FVO和3D 7等位基因的组合，其中按重量计等量的四种蛋白质中的每一种混合，结合到Alhydrogel®上，并与佐剂CPG 7909一起施用。30名志愿者入组两个剂量组，其中15名志愿者在第0、56和180天接受最多3次40 µg总蛋白给药，15名志愿者按照相同方案接受最多3次160 µg蛋白给药。大多数相关不良事件为轻度或中度，但有4名志愿者出现严重全身反应，2名志愿者因不良事件退出疫苗接种。用高剂量制剂接种两次疫苗后，AMA 1的几何平均抗体水平为136 µg/ml，MSP 142的几何平均抗体水平为78 µg/ml。高剂量组与低剂量组的抗体应答无显著差异，第三次接种后未进一步增加。证明了体外生长抑制，并且与抗AMA 1抗体应答密切相关。目前正在疟疾暴露成人中进行1b期试验。Clinicaltrials.gov www.example.com
A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of the blood stage malaria vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination of the FVO and 3D7 alleles of recombinant AMA1 and MSP142, with equal amounts by weight of each of the four proteins mixed, bound to Alhydrogel®, and administered with the adjuvant CPG 7909. Thirty (30) volunteers were enrolled in two dose groups, with 15 volunteers receiving up to three doses of 40 µg total protein at Days 0, 56, and 180, and 15 volunteers receiving up to three doses of 160 µg protein on the same schedule. Most related adverse events were mild or moderate, but 4 volunteers experienced severe systemic reactions and two were withdrawn from vaccinations due to adverse events. Geometric mean antibody levels after two vaccinations with the high dose formulation were 136 µg/ml for AMA1 and 78 µg/ml for MSP142. Antibody responses were not significantly different in the high dose versus low dose groups and did not further increase after third vaccination. In vitro growth inhibition was demonstrated and was closely correlated with anti-AMA1 antibody responses. A Phase 1b trial in malaria-exposed adults is being conducted. Clinicaltrials.gov NCT00889616
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影响因子：
3.7
作者：
Mullen GE;Ellis RD;Miura K;Malkin E;Nolan C;Hay M;Fay MP;Saul A;Zhu D;Rausch K;Moretz S;Zhou H;Long CA;Miller LH;Treanor J
通讯作者：
Treanor J
影响因子：
5.5
作者：
Genton, B;Al-Yaman, F;Alpers, MP
通讯作者：
Alpers, MP
影响因子：
3.7
作者：
Ogutu BR;Apollo OJ;McKinney D;Okoth W;Siangla J;Dubovsky F;Tucker K;Waitumbi JN;Diggs C;Wittes J;Malkin E;Leach A;Soisson LA;Milman JB;Otieno L;Holland CA;Polhemus M;Remich SA;Ockenhouse CF;Cohen J;Ballou WR;Martin SK;Angov E;Stewart VA;Lyon JA;Heppner DG;Withers MR;MSP-1 Malaria Vaccine Working Group
通讯作者：
MSP-1 Malaria Vaccine Working Group
影响因子：
3.7
作者：
Ellis RD;Martin LB;Shaffer D;Long CA;Miura K;Fay MP;Narum DL;Zhu D;Mullen GE;Mahanty S;Miller LH;Durbin AP
通讯作者：
Durbin AP
影响因子：
3.7
作者：
Lyon, Jeffrey A.;Angov, Evelina;Barnwell, John W.
通讯作者：
Barnwell, John W.