Université de Paris, Inserm, Biologie Intégrée du Globule Rouge, Paris, France.
Institut National de la Transfusion Sanguine, Paris, France.
Front Immunol. 2021 Feb 25;12:634508. doi: 10.3389/fimmu.2021.634508. eCollection 2021.
In areas where transmission is endemic, clinical immunity against malaria is progressively acquired during childhood and adults are usually protected against the severe clinical consequences of the disease. Nevertheless, pregnant women, notably during their first pregnancies, are susceptible to placental malaria and the associated serious clinical outcomes. Placental malaria is characterized by the massive accumulation of infected erythrocytes and monocytes in the placental intervillous spaces leading to maternal anaemia, hypertension, stillbirth and low birth weight due to premature delivery, and foetal growth retardation. Remarkably, the prevalence of placental malaria sharply decreases with successive pregnancies. This protection is associated with the development of antibodies directed towards the surface of -infected erythrocytes from placental origin. Placental sequestration is mediated by the interaction between VAR2CSA, a member of the erythrocyte membrane protein 1 family expressed on the infected erythrocytes surface, and the placental receptor chondroitin sulfate A. VAR2CSA stands today as the leading candidate for a placental malaria vaccine. We recently reported the safety and immunogenicity of two VAR2CSA-derived placental malaria vaccines (PRIMVAC and PAMVAC), spanning the chondroitin sulfate A-binding region of VAR2CSA, in both malaria-naïve and -exposed non-pregnant women in two distinct Phase I clinical trials (ClinicalTrials.gov, NCT02658253 and NCT02647489). This review discusses recent advances in placental malaria vaccine development, with a focus on the recent clinical data, and discusses the next clinical steps to undertake in order to better comprehend vaccine-induced immunity and accelerate vaccine development.
在疟疾流行地区，儿童在成长过程中会逐渐获得针对疟疾的临床免疫力，而成人通常能免受疟疾的严重临床影响。然而，孕妇，尤其是初次怀孕的孕妇，容易受到胎盘疟疾及其相关严重临床后果的影响。胎盘疟疾的特征是大量感染的红细胞和单核细胞在胎盘绒毛间隙中积聚，导致孕妇贫血、高血压、死产和早产导致的低出生体重，以及胎儿生长迟缓。值得注意的是，随着妊娠次数的增加，胎盘疟疾的患病率急剧下降。这种保护作用与针对胎盘来源的感染红细胞表面的抗体的发展有关。胎盘的隔离是通过 VAR2CSA（红细胞膜蛋白 1 家族的一个成员）与胎盘受体硫酸乙酰肝素 A 之间的相互作用介导的。VAR2CSA 目前是胎盘疟疾疫苗的主要候选物。我们最近报告了两种源自 VAR2CSA 的胎盘疟疾疫苗（PRIMVAC 和 PAMVAC）的安全性和免疫原性，这两种疫苗涵盖了 VAR2CSA 上硫酸乙酰肝素 A 结合区，在两项不同的 I 期临床试验中，纳入了疟疾初治和曾感染但未怀孕的女性（ClinicalTrials.gov，NCT02658253 和 NCT02647489）。本文讨论了胎盘疟疾疫苗开发的最新进展，重点介绍了最近的临床数据，并讨论了为了更好地理解疫苗诱导的免疫并加速疫苗开发而需要采取的下一步临床措施。
