Synergy in anti malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density
Synergy in anti malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density
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DOI：
10.7554/elife.35213
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发表时间：
2018-06-19
期刊：
影响因子：
7.7
通讯作者：
Blagborough, Andrew M.
中科院分区：
文献类型：
--
作者：
Sherrard-Smith, Ellie;Sala, Katarzyna A.;Blagborough, Andrew M.
抗疟疾红细胞前疫苗（PEV）通过抑制人类感染来靶向传播，但目前具有部分保护作用。有人提出，但从未证明，共同接种传播阻断疫苗（TBV）将加强疟疾控制。我们假设TBV可以降低蚊子唾液腺中的寄生虫密度，从而增强PEV功效的机制。这是测试使用多代人口测定，传代伯氏疟原虫斯氏按蚊蚊子。在PEV +TBV抗体组中观察到90.8%（86.7-94.2%）的联合疗效，高于如果两种抗体独立作用的估计疗效83.3%（95%Crl 79.1-87.0%）。在较低的蚊子寄生虫负荷下观察到较高的PEV功效，包括共同施用抗子孢子和抗传播干预协同作用的第一个直接证据，在一系列TBV剂量和传播强度下增强PEV功效。将不同抗寄生虫类的部分有效疫苗结合起来，是加速消灭疟疾努力的一种务实而有力的方法。
Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7-94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% Crl 79.1-87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts.