Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer.

Transmission-blocking activity induced by malaria vaccine candidates Pfs25/Pvs25 is a direct and predictable function of antibody titer.
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DOI:
10.1186/1475-2875-6-107
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发表时间:
2007-08-08
期刊:
影响因子:
3
通讯作者:
Saul A
Saul A
中科院分区:
医学3区
文献类型:
--
作者:
Miura K;Keister DB;Muratova OV;Sattabongkot J;Long CA;Saul A

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蚊子期疟疾疫苗被设计为在人类宿主中诱导免疫应答,这将阻断寄生虫在蚊子中的生长,从而阻断寄生虫的传播。蚊子膜摄食试验(MFA)用于测试传播阻断活性(TBA),但在这种技术中不能容纳许多样品。对抗体水平和TBA之间关系的清楚理解可能允许ELISA测定用于预测TBA并协助规划疫苗开发。制备兔抗Pfs 25血清和猴抗Pvs 25血清,并通过标准化ELISA测定抗体滴度。使用疟原虫配子体(培养的恶性疟原虫或来自疟疾患者的间日疟原虫)和按蚊通过MFA测试相同血清的生物活性。抗Pfs 25和抗Pvs 25血清显示,ELISA抗体单位与每只蚊子的卵囊密度减少百分比相关(斯皮尔曼秩相关性:分别为0.934和0.616),并且当卵囊密度减少百分比相对于测试样品的抗体单位作图时,拟合双曲线。抗体水平还与未被感染的蚊子的数量相关,并且该比例可以从对照组中每只感染蚊子的卵囊数量减少和卵囊分布来计算。ELISA数据可用作MFA的替代,以评价传播阻断疫苗的效力。这将有助于评价阻断传播疫苗和执行这一疟疾控制战略。
Mosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and consequently block transmission of the parasite. A mosquito membrane-feeding assay (MFA) is used to test transmission-blocking activity (TBA), but in this technique cannot accommodate many samples. A clear understanding of the relationship between antibody levels and TBA may allow ELISA determinations to be used to predict TBA and assist in planning vaccine development. Rabbit anti-Pfs25 sera and monkey anti-Pvs25 sera were generated and the antibody titers were determined by a standardized ELISA. The biological activity of the same sera was tested by MFA using Plasmodium gametocytes (cultured Plasmodium falciparum or Plasmodium vivax from malaria patients) and Anopheles mosquitoes. Anti-Pfs25 and anti-Pvs25 sera showed that ELISA antibody units correlate with the percent reduction in the oocyst density per mosquito (Spearman Rank correlations: 0.934 and 0.616, respectively), and fit a hyperbolic curve when percent reduction in oocyst density is plotted against antibody units of the tested sample. Antibody levels also correlated with the number of mosquitoes that failed to become infected, and this proportion can be calculated from the reduction in oocyst numbers and the distribution of oocysts per infected mosquito in control group. ELISA data may be used as a surrogate for the MFA to evaluate transmission-blocking vaccine efficacy. This will facilitate the evaluation of transmission-blocking vaccines and implementation of this malaria control strategy.
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