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
Affiliations
Daniel Wright
KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kilifi, Kenya; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; Corresponding author
Elizabeth R. Allen
Wellcome Centre for Human Genetics, Division of Structural Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Madeleine H.A. Clark
London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
John N. Gitonga
KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kilifi, Kenya
Henry K. Karanja
KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kilifi, Kenya
Ruben J.G. Hulswit
Wellcome Centre for Human Genetics, Division of Structural Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Iona Taylor
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Sumi Biswas
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Jennifer Marshall
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Damaris Mwololo
International Livestock Research Institute, PO Box 30709, Nairobi 00100, Kenya
John Muriuki
International Livestock Research Institute, PO Box 30709, Nairobi 00100, Kenya
Bernard Bett
International Livestock Research Institute, PO Box 30709, Nairobi 00100, Kenya
Thomas A. Bowden
Wellcome Centre for Human Genetics, Division of Structural Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
George M. Warimwe
KEMRI-Wellcome Trust Research Programme, CGMRC, PO Box 230-80108, Kilifi, Kenya; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford OX3 7FZ, UK
Summary: 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.
