Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wright, Daniel, Allen, Elizabeth R., Clark, Madeleine H.A., Gitonga, John N., Karanja, Henry K., Hulswit, Ruben J.G., Taylor, Iona, Biswas, Sumi, Marshall, Jennifer, Mwololo, Damaris, Muriuki, John, Bett, Bernard, Bowden, Thomas A., Warimwe, George M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588868/
https://www.ncbi.nlm.nih.gov/pubmed/33134899
http://dx.doi.org/10.1016/j.isci.2020.101669
_version_ 1783600451426451456
author Wright, Daniel
Allen, Elizabeth R.
Clark, Madeleine H.A.
Gitonga, John N.
Karanja, Henry K.
Hulswit, Ruben J.G.
Taylor, Iona
Biswas, Sumi
Marshall, Jennifer
Mwololo, Damaris
Muriuki, John
Bett, Bernard
Bowden, Thomas A.
Warimwe, George M.
author_facet Wright, Daniel
Allen, Elizabeth R.
Clark, Madeleine H.A.
Gitonga, John N.
Karanja, Henry K.
Hulswit, Ruben J.G.
Taylor, Iona
Biswas, Sumi
Marshall, Jennifer
Mwololo, Damaris
Muriuki, John
Bett, Bernard
Bowden, Thomas A.
Warimwe, George M.
author_sort Wright, Daniel
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7588868
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-75888682020-10-30 Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein Wright, Daniel Allen, Elizabeth R. Clark, Madeleine H.A. Gitonga, John N. Karanja, Henry K. Hulswit, Ruben J.G. Taylor, Iona Biswas, Sumi Marshall, Jennifer Mwololo, Damaris Muriuki, John Bett, Bernard Bowden, Thomas A. Warimwe, George M. iScience Article 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. Elsevier 2020-10-14 /pmc/articles/PMC7588868/ /pubmed/33134899 http://dx.doi.org/10.1016/j.isci.2020.101669 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Wright, Daniel
Allen, Elizabeth R.
Clark, Madeleine H.A.
Gitonga, John N.
Karanja, Henry K.
Hulswit, Ruben J.G.
Taylor, Iona
Biswas, Sumi
Marshall, Jennifer
Mwololo, Damaris
Muriuki, John
Bett, Bernard
Bowden, Thomas A.
Warimwe, George M.
Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein
title Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein
title_full Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein
title_fullStr Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein
title_full_unstemmed Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein
title_short Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein
title_sort naturally acquired rift valley fever virus neutralizing antibodies predominantly target the gn glycoprotein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588868/
https://www.ncbi.nlm.nih.gov/pubmed/33134899
http://dx.doi.org/10.1016/j.isci.2020.101669
work_keys_str_mv AT wrightdaniel naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT allenelizabethr naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT clarkmadeleineha naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT gitongajohnn naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT karanjahenryk naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT hulswitrubenjg naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT tayloriona naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT biswassumi naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT marshalljennifer naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT mwololodamaris naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT muriukijohn naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT bettbernard naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT bowdenthomasa naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein
AT warimwegeorgem naturallyacquiredriftvalleyfevervirusneutralizingantibodiespredominantlytargetthegnglycoprotein