Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.
Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.
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DOI：
10.1371/journal.pone.0002940
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发表时间：
2008-08-13
期刊：
影响因子：
3.7
通讯作者：
Treanor J
中科院分区：
文献类型：
--
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
顶端膜抗原1（AMA 1）是一种多态性裂殖子表面蛋白，是一种领先的血液阶段疟疾疫苗候选者。这是首次报道的研究性疫苗AMA 1-C1/Alhydrogel与新型佐剂CPG 7909在人类中的应用。在罗切斯特大学进行了一项1期试验，有75名疟疾初治志愿者参加，以评估AMA 1-C1/Alhydrogel+CPG 7909疟疾疫苗的安全性和免疫原性。参与者按顺序入组并在剂量递增队列中随机化，以在第0、28和56天接受20 μg AMA 1-C1/Alhydrogel®+564 μg CPG 7909（n = 15）、80 μg AMA 1-C1/Alhydrogel®（n = 30）或80 μg AMA 1-C1/Alhydrogel+564 μg CPG 7909（n = 30）的三次疫苗接种。 加入CPG 7909后，局部和全身不良事件的严重程度明显更高。通过酶联免疫吸附试验（ELISA）检测抗AMA 1免疫球蛋白G（IgG），与单独使用80 µg AMA 1-C1/Alhydrogel相比，接受20 µg或80 µg AMA 1-C1/Alhydrogel+CPG 7909的志愿者的免疫血清中抗AMA 1抗体浓度显着增加高达14倍。将CPG 7909添加到人体中的AMA 1-C1/Alhydrogel疫苗中还引发AMA 1特异性免疫IgG，其显著且显著地增加同源寄生虫的体外生长抑制至高达96%的抑制水平。鉴于观察到免疫原性显著增加，AMA 1-C1/Alhydrogel+CPG 7909疟疾疫苗的安全性特征是可接受的。进一步的临床开发正在进行中。ClinicalTrials.gov NCT00344539
Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909. A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 µg of AMA1-C1/Alhydrogel®+564 µg CPG 7909 (n = 15), 80 µg of AMA1-C1/Alhydrogel® (n = 30), or 80 µg of AMA1-C1/Alhydrogel+564 µg CPG 7909 (n = 30). Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA), and the immune sera of volunteers that received 20 µg or 80 µg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 µg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition. The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing. ClinicalTrials.gov NCT00344539
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DOI：
10.1073/pnas.0701464104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Dutta, Sheetij;Lee, Seung Yeon;Lanar, David E.
通讯作者：
Lanar, David E.
影响因子：
1.5
作者：
Escalante, AA;Grebert, HM;Lal, AA
通讯作者：
Lal, AA
影响因子：
1.5
作者：
Marshall, VM;Zhang, LX;Coppel, RL
通讯作者：
Coppel, RL
影响因子：
5.5
作者：
Mullen, Gregory E. D.;Aebig, Joan A.;Saul, Allan
通讯作者：
Saul, Allan
影响因子：
3.1
作者：
Narum, DL;Ogun, SA;Holder, AA
通讯作者：
Holder, AA