Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein

Daniel Wright; Elizabeth R Allen; Madeleine H A Clark; John N Gitonga; Henry K Karanja; Ruben J G Hulswit; Iona Taylor; Sumi Biswas; Jennifer Marshall; Damaris Mwololo; John Muriuki; Bernard Bett; Thomas A Bowden; George M Warimwe

doi:10.1016/j.isci.2020.101669

Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein

iScience. 2020 Oct 14;23(11):101669. doi: 10.1016/j.isci.2020.101669. eCollection 2020 Nov 20.

Authors

Affiliations

¹ KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kilifi, Kenya.
² The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
³ Wellcome Centre for Human Genetics, Division of Structural Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
⁴ London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
⁵ International Livestock Research Institute, PO Box 30709, Nairobi 00100, Kenya.
⁶ Centre for Tropical Medicine and Global Health, University of Oxford, Oxford OX3 7FZ, UK.

Abstract

Rift Valley fever (RVF) is a viral hemorrhagic 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 (nAbs) 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.

Keywords: Immunology; Virology.

Abstract

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