Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies

Kimberley Steeds; Yper Hall; Gillian S. Slack; Stephanie Longet; Thomas Strecker; Sarah Katharina Fehling; Edward Wright; Joseph Akoi Bore; Fara Raymond Koundouno; Mandy Kader Konde; Roger Hewson; Julian A. Hiscox; Georgios Pollakis; Miles Carroll

doi:10.1038/s41598-020-71225-1

Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies

Kimberley Steeds, Yper Hall, Gillian S. Slack, Stephanie Longet, Thomas Strecker, Sarah Katharina Fehling, Edward Wright, Joseph Akoi Bore, Fara Raymond Koundouno, Mandy Kader Konde, Roger Hewson, Julian A. Hiscox, Georgios Pollakis, Miles Carroll^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV.

Original language	English
Article number	14289
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-71225-1
Publication status	Published - 1 Dec 2020

Bibliographical note

Funding Information:
The authors would like to thank Masayuki Saijo for providing the rVSV-ΔG-Luc-VSV-G virus and anti-VSV-G hybridoma cell culture supernatant. We are grateful to ECCAC for providing Vero E6 and HeLa cells, and to Arvind Patel for providing Huh-7 cells. This work was funded by the U.S. Food and Drug Administration (FDA) (Contract No. HHSF223201510104C) and by Horizon 2020 EU, project EVIDENT (Grant Agreement No. 666100). T.S received funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (Project No. 197785619/SFB1021). Permission for the study was granted by the Guinea Comite National D’Ethique Pour La Recherche en Sante (No. 33/CNERS/15).

Publisher Copyright:
© 2020, The Author(s).

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

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Steeds, K., Hall, Y., Slack, G. S., Longet, S., Strecker, T., Fehling, S. K., Wright, E., Bore, J. A., Koundouno, F. R., Konde, M. K., Hewson, R., Hiscox, J. A., Pollakis, G., & Carroll, M. (2020). Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies. Scientific Reports, 10(1), Article 14289. https://doi.org/10.1038/s41598-020-71225-1

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title = "Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies",

abstract = "Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV.",

author = "Kimberley Steeds and Yper Hall and Slack, {Gillian S.} and Stephanie Longet and Thomas Strecker and Fehling, {Sarah Katharina} and Edward Wright and Bore, {Joseph Akoi} and Koundouno, {Fara Raymond} and Konde, {Mandy Kader} and Roger Hewson and Hiscox, {Julian A.} and Georgios Pollakis and Miles Carroll",

note = "Funding Information: The authors would like to thank Masayuki Saijo for providing the rVSV-ΔG-Luc-VSV-G virus and anti-VSV-G hybridoma cell culture supernatant. We are grateful to ECCAC for providing Vero E6 and HeLa cells, and to Arvind Patel for providing Huh-7 cells. This work was funded by the U.S. Food and Drug Administration (FDA) (Contract No. HHSF223201510104C) and by Horizon 2020 EU, project EVIDENT (Grant Agreement No. 666100). T.S received funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (Project No. 197785619/SFB1021). Permission for the study was granted by the Guinea Comite National D{\textquoteright}Ethique Pour La Recherche en Sante (No. 33/CNERS/15). Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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Steeds, K, Hall, Y, Slack, GS, Longet, S, Strecker, T, Fehling, SK, Wright, E, Bore, JA, Koundouno, FR, Konde, MK, Hewson, R, Hiscox, JA, Pollakis, G & Carroll, M 2020, 'Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies', Scientific Reports, vol. 10, no. 1, 14289. https://doi.org/10.1038/s41598-020-71225-1

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AU - Slack, Gillian S.

AU - Longet, Stephanie

AU - Strecker, Thomas

AU - Fehling, Sarah Katharina

AU - Wright, Edward

AU - Bore, Joseph Akoi

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AU - Konde, Mandy Kader

AU - Hewson, Roger

AU - Hiscox, Julian A.

AU - Pollakis, Georgios

AU - Carroll, Miles

N1 - Funding Information: The authors would like to thank Masayuki Saijo for providing the rVSV-ΔG-Luc-VSV-G virus and anti-VSV-G hybridoma cell culture supernatant. We are grateful to ECCAC for providing Vero E6 and HeLa cells, and to Arvind Patel for providing Huh-7 cells. This work was funded by the U.S. Food and Drug Administration (FDA) (Contract No. HHSF223201510104C) and by Horizon 2020 EU, project EVIDENT (Grant Agreement No. 666100). T.S received funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (Project No. 197785619/SFB1021). Permission for the study was granted by the Guinea Comite National D’Ethique Pour La Recherche en Sante (No. 33/CNERS/15). Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

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AB - Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV.

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Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies

Abstract

Bibliographical note

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