a plasma survey using 38 pfemp1 domains reveals frequent recognition of the plasmodium falciparum antigen var2csa among young tanzanian children等离子体调查使用38 pfemp1域显示频繁的恶性疟原虫抗原var2csa年轻人坦桑尼亚的孩子.pdfVIP

A Plasma Survey Using 38 PfEMP1 Domains Reveals Frequent Recognition of the Plasmodium falciparum Antigen VAR2CSA among Young Tanzanian Children 1 1 1 1 1 Andrew V. Oleinikov *, Valentina V. Voronkova , Isaac Tyler Frye , Emily Amos , Robert Morrison , Michal Fried1,2,3, Patrick E. Duffy1,2,3 1 Seattle Biomedical Research Institute, Seattle, Washington, United States of America, 2 Department of Global Health, University of Washington, Seattle, Washington, United States of America, 3 Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases/NIH, Rockville, Maryland, United States of America Abstract PfEMP1 proteins comprise a family of variant antigens that appear on the surface of P. falciparum-infected erythrocytes and bind to multiple host receptors. Using a mammalian expression system and BioPlex technology, we developed an array of 24 protein constructs representing 38 PfEMP1 domains for high throughput analyses of receptor binding as well as total and functional antibody responses. We analyzed the reactivity of 561 plasma samples from 378 young Tanzanian children followed up to maximum 192 weeks of life in a longitudinal birth cohort. Surprisingly, reactivity to the DBL5 domain of VAR2CSA, a pregnancy malaria vaccine candidate, was most common, and the prevalence of reactivity was stable throughout early childhood. Reactivity to all other PfEMP1 constructs increased with age. Antibodies to the DBL2bC2PF11_0521 domain, measured as plasma reactivity or plasma inhibition of ICAM1 binding, predicted reduced risk of hospitalization for severe or moderately severe malaria. These data su