Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge.
Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge.
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DOI：
10.1371/journal.pone.0131456
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fischer R
中科院分区：
文献类型：
--
作者：
Boes A;Spiegel H;Voepel N;Edgue G;Beiss V;Kapelski S;Fendel R;Scheuermayer M;Pradel G;Bolscher JM;Behet MC;Dechering KJ;Hermsen CC;Sauerwein RW;Schillberg S;Reimann A;Fischer R
在多阶段特异性混合物的背景下组合来自恶性疟原虫生命周期的不同阶段的关键抗原提供了一种有希望的方法，用于开发理想地能够预防初始感染、临床表现以及疾病传播的疟疾疫苗。为了研究这种方法的潜力，我们将来自恶性疟原虫的红细胞前、血液和性阶段的蛋白质和结构域（总共11个）组合成植物中重组产生的四种不同组分的混合物。免疫家兔后，我们测定了结构域特异性抗体滴度以及组分特异性抗体浓度，并将其与阶段特异性体外效力相关联。使用纯化的兔免疫IgG，我们在功能性体外测定中观察到强烈的抑制作用，该测定涉及红细胞前（高达80%）、血液（高达90%）和性寄生虫阶段（100%）。根据成分特异性抗体浓度，我们计算了红细胞前期（17-25 μg/ml）、血液期（40-60 μg/ml）和性期（1.75 μg/ml）的IC 50值。虽然结果强调了多阶段疫苗鸡尾酒的可行性，但组分特异性功效的分析表明，阶段特异性抗体浓度的IC 50要求存在显著差异，这为这种复杂情况提供了有价值的见解，从而将改善疟疾疫苗鸡尾酒开发的未来方法，包括选择合适的抗原和组分比例，以微调整体和阶段特异性功效。
Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17–25 μg/ml), the blood stage (40–60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.
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影响因子：
13.8
作者：
Boes, Alexander;Spiegel, Holger;Fischer, Rainer
通讯作者：
Fischer, Rainer
影响因子：
3.1
作者：
Gantt, S;Persson, C;Nussenzweig, V
通讯作者：
Nussenzweig, V
影响因子：
6.4
作者：
AMADOR, R;MORENO, A;PATARROYO, ME
通讯作者：
PATARROYO, ME
影响因子：
3.1
作者：
Fischer, Rainer;Schillberg, Stefan;Twyman, Richard M.
通讯作者：
Twyman, Richard M.
DOI：
10.1084/jem.172.1.379
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blackman MJ;Heidrich HG;Donachie S;McBride JS;Holder AA
通讯作者：
Holder AA