Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya.
Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya.
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DOI：
10.1371/journal.pone.0004708
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
MSP-1 Malaria Vaccine Working Group
中科院分区：
文献类型：
--
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
恶性疟蛋白1(FMP1)代表恶性疟原虫3D7克隆裂殖子表面蛋白1(MSP-1)的42 kDa C末端片段。它由AS02(一种专有佐剂系统)配制而成，构成了FMP1/AS02候选疟疾疫苗。我们评估了这种疫苗在非洲儿童中的安全性、免疫原性和有效性。这是一项随机、双盲、IIb期对照试验，在肯尼亚西部Nyanza省Kombewa分部内1英里半径的13个野外站点进行，Kombewa分部是恶性疟原虫全地方性传播的地区。我们招募了400名12-47个月大的健康儿童。儿童以1：1的方式随机接种FMP1/AS02(50微克)或Rabipur®狂犬病疫苗。疫苗接种按0、1和2个月的时间表进行。主要研究终点是第三次接种后14天至6个月之间发生的恶性疟原虫首次临床发作的时间(体温≥37.5°C，无性寄生虫血症≥50,000条寄生虫/微克L血液)。病例侦破既有主动也有被动。在第一次免疫后的8个月内评估安全性和免疫原性；在第三次接种后的6个月内测量疫苗效力(VE)。400名儿童中有374人接受了所有三种剂量的治疗，并完成了6个月的随访。FMP1/AS02具有良好的安全性，耐受性良好，但比对照试剂更具反应性。在FMP1/AS02受体中，抗MSP-142抗体的几何平均浓度从1.3微克/毫升增加到27.3微克/毫升，但在对照组中没有变化。FMP1/AS02组97名儿童和对照组98名儿童有主要终点发作。总体VE为5.1%(95%CI：−为26%至+28%；p值 = 为0.7)。FMP1/AS02不是作为单价疟疾疫苗进一步开发的有希望的候选者。未来MSP-142疫苗的开发应该集中在其他配方和抗原结构上。ClinicalTrials.gov NCT00223990
The antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children. A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12–47 months in general good health.Children were randomised in a 1∶1 fashion to receive either FMP1/AS02 (50 µg) or Rabipur® rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature ≥37.5°C with asexual parasitaemia of ≥50,000 parasites/µL of blood) occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE) was measured over a six-month period following third vaccinations. 374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-142 antibody concentrations increased from1.3 µg/mL to 27.3 µg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: −26% to +28%; p-value = 0.7). FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-142 vaccine development should focus on other formulations and antigen constructs. Clinicaltrials.gov NCT00223990
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DOI：
10.1084/jem.186.10.1689
发表时间：
1997-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guevara Patiño JA;Holder AA;McBride JS;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
3.1
作者：
Shi, YP;Sayed, U;Lal, AA
通讯作者：
Lal, AA
影响因子：
3.1
作者：
Corran, PH;O'Donnell, RA;Riley, EM
通讯作者：
Riley, EM
影响因子：
6.4
作者：
Egan, AF;Morris, J;Riley, EM
通讯作者：
Riley, EM
影响因子：
1.5
作者：
Angov, E;Aufiero, BM;Lyon, JA
通讯作者：
Lyon, JA