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Naturally acquired Rift Valley fever virus neutralizing antibodies predominantly target the Gn glycoprotein
medRxiv - Allergy and Immunology Pub Date : 2020-08-11 , DOI: 10.1101/2020.08.07.20170241
Daniel Wright , Elizabeth R. Allen , Madeleine H.A. Clark , John N. Gitonga , Henry K. Karanja , Ruben Hulswit , Iona Taylor , Sumi Biswas , Jennifer Marshall , Damaris Mwololo , John Muriuki , Bernard Bett , Thomas A. Bowden , George M. Warimwe

Rift Valley fever (RVF) is a viral haemorrhagic disease first discovered in Kenya in 1930. Numerous animal studies have demonstrated that protective immunity is acquired following RVF virus (RVFV) infection, and that this correlates with acquisition of virus neutralizing antibodies (nAb) that target the viral envelope glycoproteins. However, naturally acquired immunity to RVF in humans is poorly described. Here, we characterized the immune response to the viral envelope glycoproteins, Gn and Gc, in RVFV-exposed Kenyan adults. Long-lived IgG (dominated by IgG1 subclass) and T cell responses were detected against both Gn and Gc. However, antigen-specific antibody depletion experiments showed that Gn-specific antibodies dominate the RVFV nAb response. IgG avidity against Gn, but not Gc, correlated with nAb titers. These data are consistent with the greater level of immune accessibility of Gn on the viral envelope surface and confirm the importance of Gn as an integral component for RVF vaccine development.

中文翻译:

自然获得的裂谷热病毒中和抗体主要靶向Gn糖蛋白

裂谷热(RVF)是一种病毒性出血性疾病,最早于1930年在肯尼亚发现。大量动物研究表明,在RVF病毒(RVFV)感染后可获得保护性免疫力,这与获得病毒中和抗体(nAb)有关靶向病毒包膜糖蛋白。但是,人类对RVF的自然获得的免疫力描述不佳。在这里,我们表征了暴露于RVFV的肯尼亚成年人对病毒包膜糖蛋白Gn和Gc的免疫应答。检测到针对Gn和Gc的长寿命IgG(主要由IgG1亚类)和T细胞应答。但是,抗原特异性抗体耗竭实验表明,Gn特异性抗体主导RVFV nAb反应。IgG对Gn(而非Gc)的亲和力与nAb滴度相关。
更新日期:2020-08-11
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