Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.
Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.
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DOI：
10.1371/journal.pone.0008787
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发表时间：
2010-01-22
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;Martin LB;Shaffer D;Long CA;Miura K;Fay MP;Narum DL;Zhu D;Mullen GE;Mahanty S;Miller LH;Durbin AP
Merozoite surface protein 142 （MSP142）是一种主要的血期疟疾候选疫苗。为了诱导覆盖主要抗原多态性的免疫应答，将MSP142的FVO和3D7重组蛋白混合（MSP142- c1）。为了提高抗体应答水平，MSP142-C1用Alhydrogel加新型佐剂CPG 7909配制。华盛顿特区免疫研究中心在健康malaria-naïve成人中进行了一项1期临床试验，以评估MSP142-C1/醛水凝胶+/−CPG 7909的安全性和免疫原性。60名志愿者被纳入剂量递增队列，在0、1和2个月时随机接受3次疫苗接种，分别为40或160µg蛋白质吸附在Alhydrogel +/ - 560µg CPG 7909上。疫苗接种耐受性良好，只有一个相关不良事件分级为严重（3级注射部位红斑），所有其他疫苗相关不良事件分级为轻度或中度。局部不良事件在CPG组更为频繁和严重。与单独使用MSP142-C1/Alhydrogel相比，CPG在第二次免疫后两周增强了抗msp142抗体应答，在第三次免疫后两周增强了49倍（p<0.0001）。第三次免疫后，通过体外生长抑制试验检测抗体的功能。抑制作用是抗体滴度的函数，非CPG组平均为3%（范围为- 2至10%），而CPG组平均为14%（范围为3至32%）。MSP142-C1/Alhydrogel + CPG 7909诱导的良好安全性和高抗体应答令人鼓舞。MSP142-C1/醛水凝胶正在与其他血期抗原联合，并将在与CPG 7909佐剂的制剂中推进。ClinicalTrials.gov标识符：NCT00320658
Merozoite surface protein 142 (MSP142) is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP142 were mixed (MSP142-C1). To improve the level of antibody response, MSP142-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909. A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP142-C1/Alhydrogel +/− CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 µg protein adsorbed to Alhydrogel +/− 560 µg CPG 7909 at 0, 1 and 2 months. Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema) and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP142 antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP142-C1/Alhydrogel alone (p<0.0001). After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range −2 to 10%) in the non CPG groups versus 14% (3 to 32%) in the CPG groups. The favorable safety profile and high antibody responses induced with MSP142-C1/Alhydrogel + CPG 7909 are encouraging. MSP142-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909. ClinicalTrials.gov Identifier: NCT00320658
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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：
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：
Lyon, Jeffrey A.;Angov, Evelina;Barnwell, John W.
通讯作者：
Barnwell, John W.
第1阶段的研究对恶性疟原虫疟疾的两种蛋白石表面蛋白1（MSP1（42））疫苗的研究。
DOI：
10.1371/journal.pctr.0020012
发表时间：
2007
期刊：
PLOS CLINICAL TRIALS
影响因子：
--
作者：
Malkin, Elissa;Long, Carole A;Stowers, Anthony W;Zou, Lanling;Singh, Sanjay;MacDonald, Nicholas J;Narum, David L;Miles, Aaron P;Orcutt, Andrew C;Muratova, Olga;Moretz, Samuel E;Zhou, Hong;Diouf, Ababacar;Fay, Michael;Tierney, Eveline;Leese, Philip;Mahanty, Siddhartha;Miller, Louis H;Saul, Allan;Martin, Laura B
通讯作者：
Martin, Laura B
影响因子：
9.1
作者：
Cooper, CL;Davis, HL;Heathcote, J
通讯作者：
Heathcote, J