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Placental malaria vaccine candidate antigen VAR2CSA displays atypical domain architecture in some Plasmodium falciparum strains.
Communications Biology ( IF 5.2 ) Pub Date : 2019-12-06 , DOI: 10.1038/s42003-019-0704-z
Justin Y A Doritchamou 1 , Robert Morrison 1 , Jonathan P Renn 1 , Jose Ribeiro 2 , Junhui Duan 1 , Michal Fried 1 , Patrick E Duffy 1
Affiliation  

Two vaccines based on Plasmodium falciparum protein VAR2CSA are currently in clinical evaluation to prevent placental malaria (PM), but a deeper understanding of var2csa variability could impact vaccine design. Here we identified atypical extended or truncated VAR2CSA extracellular structures and confirmed one extended structure in a Malian maternal isolate, using a novel protein fragment assembly method for RNA-seq and DNA-seq data. Extended structures included one or two additional DBL domains downstream of the conventional NTS-DBL1X-6ɛ domain structure, with closest similarity to DBLɛ in var2csa and non-var2csa genes. Overall, 4/82 isolates displayed atypical VAR2CSA structures. The maternal isolate expressing an extended VAR2CSA bound to CSA, but its recombinant VAR2CSA bound less well to CSA than VAR2CSANF54 and showed lower reactivity to naturally acquired parity-dependent antibody. Our protein fragment sequence assembly approach has revealed atypical VAR2CSA domain architectures that impact antigen reactivity and function, and should inform the design of VAR2CSA-based vaccines.

中文翻译:


胎盘疟疾疫苗候选抗原 VAR2CSA 在一些恶性疟原虫菌株中表现出非典型结构域结构。



两种基于恶性疟原虫蛋白 VAR2CSA 的疫苗目前正在进行临床评估,以预防胎盘疟疾 (PM),但对 var2csa 变异性的更深入了解可能会影响疫苗设计。在这里,我们使用一种新的 RNA-seq 和 DNA-seq 数据蛋白质片段组装方法,鉴定了非典型的延伸或截短的 VAR2CSA 胞外结构,并确认了马里母体分离株中的一个延伸结构。扩展结构包括传统 NTS-DBL1X-6ɛ 结构域下游的一两个额外的 DBL 结构域,与 var2csa 和非 var2csa 基因中的 DBLɛ 最相似。总体而言,4/82 个分离株表现出非典型的 VAR2CSA 结构。表达延伸的VAR2CSA的母本分离株与CSA结合,但其重组VAR2CSA与CSA的结合不如VAR2CSANF54好,并且对自然获得的奇偶依赖性抗体表现出较低的反应性。我们的蛋白质片段序列组装方法揭示了影响抗原反应性和功能的非典型 VAR2CSA 结构域结构,并且应该为基于 VAR2CSA 的疫苗的设计提供信息。
更新日期:2019-12-06
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