Identifying the targets of protective immunity to malaria in pregnancy

妊娠期疟疾是许多国家疾病的主要原因。孕妇患疟疾的风险很高，大量疟疾寄生虫在胎盘中积聚，这可能导致婴儿或产妇死亡。疟疾寄生虫通过产生能够附着在胎盘上的蛋白质来感染胎盘。这些引起胎盘感染的疟疾毒株一般不会在未怀孕的个体中引起疾病。针对这种寄生虫蛋白的抗体是在胎盘感染时产生的，这可能有助于控制感染并防止妊娠期间进一步感染疟疾。然而，胎盘疟原虫能够改变它们产生的蛋白质以避免免疫反应。在这个项目中，我们将研究导致妊娠期疟疾的寄生虫菌株，以及保护孕妇免受疟疾及其并发症侵害的抗体的开发。我们的目标是确定寄生虫用来附着在胎盘上的基因和蛋白质，并确定这些蛋白质发生了多少变化。我们还将专门研究一种名为var2csa的特定候选基因及其蛋白质的作用，因为它最近与妊娠疟疾有关。我们将研究识别不同蛋白质和不同形式的疟疾寄生虫的抗体是如何产生的，并确定在非洲马拉维参加一项关于妊娠期疟疾的纵向研究的孕妇的抗体类型。我们还将研究怀孕期间服用抗疟疾药物如何影响保护性抗体的产生。通过这些研究，我们的目标是了解免疫系统如何在怀孕期间对抗疟疾。这对于开发预防或治疗妊娠期疟疾的新方法以及改善儿童和孕产妇健康至关重要。

Malaria in pregnancy is a major cause of disease across many countries. Pregnant women have a high risk of malaria, and large numbers of malaria parasites accumulate in the placenta, which may lead to infant or maternal death. Malaria parasites infect the placenta by producing proteins that enable them to stick to the placenta. These malaria strains causing placental infection generally do not cause disease in non-pregnant individuals. Antibodies to the parasite proteins are produced in response to placental infection, which may help control the infection and protect against further malaria in pregnancy. However, placental malaria parasites are able to vary the proteins they produce to avoid immune responses. In this project, we will study the parasite strains that cause malaria in pregnancy and the development of antibodies that protect pregnant women against malaria and its complications. We aim to identify the genes and proteins that parasites use to stick to the placenta, and determine how much variation occurs in these proteins. We will also specifically examine the role of one particular candidate gene called var2csa, and its protein, as this has been recently been associated with pregnancy malaria. We will examine how antibodies develop that recognise different proteins and different forms of malaria parasites, and determine the type of antibodies that protect pregnant women taking part in a longitudinal study of malaria in pregnancy in Malawi, Africa. We will also examine how antimalarial drugs taken in pregnancy influence the development of protective antibodies. Through these studies we aim to understand how the immune system combats malaria in pregnancy. This will be important for developing new methods for preventing or treating malaria in pregnancy, and improving child and maternal health.