Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, Maryland, USA.
J Infect Dis. 2022 Aug 26;226(3):521-527. doi: 10.1093/infdis/jiac096.
Plasmodium falciparum-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding P. falciparum CS2 parasites during the third trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with P. falciparum CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, P. falciparum infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines. Clinical Trials Registration: NCT02471378.
感染恶性疟原虫(Plasmodium falciparum)的红细胞表面表达变异表面抗原 VAR2CSA,与硫酸软骨素 A(chondroitin sulfate A,CSA)结合后被隔离在胎盘绒毛间隙,从而导致母婴的严重后遗症。本研究建立了胎盘疟疾(placental malaria,PM)猴模型。妊娠 Aotus 在妊娠晚期感染与 CSA 结合的恶性疟原虫 CS2 寄生虫,导致晚期寄生虫在表达 VAR2CSA 并特异性结合 CSA 的胎盘绒毛间隙中明显隔离。与免疫多胎孕妇相似,感染恶性疟原虫 CS2 寄生虫的猴在连续妊娠中获得针对 VAR2CSA 的抗体,其功能活性在随后的妊娠感染中增强。Aotus 在多次急性 PM 发作和随后的 VAR2CSA 免疫接种后也产生了功能性抗体。总之,妊娠 Aotus 猴感染恶性疟原虫可重现人类 PM 感染和免疫的所有显著特征,该模型可用于基础机制研究和临床前研究,以鉴定候选 PM 疫苗。临床试验注册:NCT02471378。