differential induction of functional igg using the plasmodium falciparum placental malaria vaccine candidate var2csa微分感应功能使用恶性疟原虫免疫球蛋白var2csa胎盘疟疾疫苗候选人.pdfVIP

Differential Induction of Functional IgG Using the Plasmodium falciparum Placental Malaria Vaccine Candidate VAR2CSA 1,2 1,2 1,2 1,2 ¨ 1,2 Vera V. Pinto , Sisse B. Ditlev , Kamilla E. Jensen , Mafalda Resende , Madeleine Dahlback , Gorm Andersen1,2, Pernille Andersen1,2, Thor G. Theander1,2, Ali Salanti1,2, Morten A. Nielsen1,2* 1 Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark, 2 Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark Abstract Background: In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen and chondroitin sulfate A (CSA) in the placental intervillous space and lack of protective antibodies. PM impairs fetal development mainly by excessive inflammation processes. After infections during pregnancy women acquire immunity to PM conferred by antibodies against VAR2CSA. Ideally, a vaccine against PM will induce antibody-mediated immune responses that block the adhesion of infected erythrocytes (IE) in the placenta. Principal Findings: We have previously shown that antibodies raised in rat against individual domains of VAR2CSA can block IE binding to CSA. In this study we have immunized mice, rats and rabbits with each individual domain and the full- length protein corresponding to the FCR3 VAR2CSA variant. We