Transmission-blocking activity is determined by transmission-reducing activity and number of control oocysts in Plasmodium falciparum standard membrane-feeding assay.
Transmission-blocking activity is determined by transmission-reducing activity and number of control oocysts in Plasmodium falciparum standard membrane-feeding assay.
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DOI：
10.1016/j.vaccine.2016.06.066
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发表时间：
2016-07-29
期刊：
影响因子：
5.5
通讯作者：
Long CA
中科院分区：
文献类型：
--
作者：
Miura K;Swihart BJ;Deng B;Zhou L;Pham TP;Diouf A;Burton T;Fay MP;Long CA
疟疾传播疫苗（TBV）可能是消除疟疾的有用工具。比较不同研究的结果，这是非常挑战的。蚊子（TBA）已被广泛使用。
在这项研究中，我们使用105个独立的进食实验（包括9,804个蚊子）的数据对SMFA的卵囊数据进行了统计建模。对照蚊子（Mo-contl）和TBA中的平均卵囊计数。在MO-CONTL上，无论是测试的单克隆或多克隆抗体，使用MO-CONTL和观察到的TRA的模型中观察到的TBA和预测的TBA有很强的一致性。 。无论Mo-contl如何，都可以进行多个进料的比较。
这是第一个研究表明，观察到的TBA可以通过MO-CONTL合理预测，并且使用独立的实验数据进行测试抗体。续。不同的研究，从而使未来的TBV发展受益。
Malaria transmission-blocking vaccines (TBVs) are potentially helpful tools for malaria eradication. The standard membrane-feeding assay (SMFA) is considered one of the “gold standard” assays for TBV development. However, lack of consensus in reporting results from SMFA has made it very challenging to compare results from different studies. Two main readouts, % inhibition in mean oocyst count per mosquito (TRA) and % inhibition in prevalence of infected mosquitoes (TBA), have been used widely. In this study, we statistically modeled the oocyst data in SMFA using data from 105 independent feeding experiments including 9,804 mosquitoes. The model was validated using an independent data set that included 10,790 mosquitoes from 110 feeding studies. The model delineates a relationship between TRA, the mean oocyst count in the control mosquitoes (mo-contl), and TBA. While TRA was independent from mo-contl, TBA values changed depending on mo-contl. Regardless of monoclonal or polyclonal antibodies tested, there were strong concordances between observed TBA and predicted TBA based on the model using mo-contl and observed TRA. Simulations showed that SMFA with lower true control means had increased uncertainty in TRA estimates. The strong linkage between TBA, TRA and mo-contl inspired creation of a standardized TBA, a model-based TBA standardized to a target control mean, which allows comparison across multiple feeds regardless of mo-contl. This is the first study showing that the observed TBA can be reasonably predicted by mo-contl and the TRA of the test antibody using independent experimental data. This study indicates that TRA should be used to compare results from multiple feeds with different levels of mo-contl. If a measure of TBA is desired, it is better to report standardized TBA rather than observed TBA. These recommendations support rational comparisons of results from different studies, thus benefiting future TBV development.