Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate
Abstract It has been proven challenging to conduct traditional efficacy trials for Ebola virus (EBOV) vaccines. In the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effec...
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2020-12-01
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doaj-31753f8ec19c4f7ca129201ac99ccb002020-12-20T12:22:49ZengNature Publishing Groupnpj Vaccines2059-01052020-12-015111110.1038/s41541-020-00261-9Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidateRamon Roozendaal0Jenny Hendriks1Thierry van Effelterre2Bart Spiessens3Liesbeth Dekking4Laura Solforosi5Dominika Czapska-Casey6Viki Bockstal7Jeroen Stoop8Daniel Splinter9Sarah Janssen10Ben van Baelen11Nadia Verbruggen12Jan Serroyen13Eline Dekeyster14Ariane Volkmann15Yvonne Wollmann16Ricardo Carrion17Luis D. Giavedoni18Cynthia Robinson19Maarten Leyssen20Macaya Douoguih21Kerstin Luhn22Maria Grazia Pau23Jerry Sadoff24An Vandebosch25Hanneke Schuitemaker26Roland Zahn27Benoit Callendret28Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen R&DJanssen R&DJanssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen R&DJanssen R&DJanssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Bavarian NordicBavarian NordicTexas Biomedical Research InstituteTexas Biomedical Research InstituteJanssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen R&DJanssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Janssen Vaccines & Prevention B.V.Abstract It has been proven challenging to conduct traditional efficacy trials for Ebola virus (EBOV) vaccines. In the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. We here propose to infer the protective effect of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen with an 8-week interval in humans by immunobridging. Immunogenicity and protective efficacy data were obtained for Ad26.ZEBOV and MVA-BN-Filo vaccine regimens using a fully lethal EBOV Kikwit challenge model in cynomolgus monkeys (nonhuman primates [NHP]). The association between EBOV neutralizing antibodies, glycoprotein (GP)-binding antibodies, and GP-reactive T cells and survival in NHP was assessed by logistic regression analysis. Binding antibodies against the EBOV surface GP were identified as the immune parameter with the strongest correlation to survival post EBOV challenge, and used to infer the predicted protective effect of the vaccine in humans using published data from phase I studies. The human vaccine-elicited EBOV GP-binding antibody levels are in a range associated with significant protection against mortality in NHP. Based on this immunobridging analysis, the EBOV GP-specific-binding antibody levels elicited by the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in humans will likely provide protection against EBOV disease.https://doi.org/10.1038/s41541-020-00261-9 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ramon Roozendaal Jenny Hendriks Thierry van Effelterre Bart Spiessens Liesbeth Dekking Laura Solforosi Dominika Czapska-Casey Viki Bockstal Jeroen Stoop Daniel Splinter Sarah Janssen Ben van Baelen Nadia Verbruggen Jan Serroyen Eline Dekeyster Ariane Volkmann Yvonne Wollmann Ricardo Carrion Luis D. Giavedoni Cynthia Robinson Maarten Leyssen Macaya Douoguih Kerstin Luhn Maria Grazia Pau Jerry Sadoff An Vandebosch Hanneke Schuitemaker Roland Zahn Benoit Callendret |
spellingShingle |
Ramon Roozendaal Jenny Hendriks Thierry van Effelterre Bart Spiessens Liesbeth Dekking Laura Solforosi Dominika Czapska-Casey Viki Bockstal Jeroen Stoop Daniel Splinter Sarah Janssen Ben van Baelen Nadia Verbruggen Jan Serroyen Eline Dekeyster Ariane Volkmann Yvonne Wollmann Ricardo Carrion Luis D. Giavedoni Cynthia Robinson Maarten Leyssen Macaya Douoguih Kerstin Luhn Maria Grazia Pau Jerry Sadoff An Vandebosch Hanneke Schuitemaker Roland Zahn Benoit Callendret Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate npj Vaccines |
author_facet |
Ramon Roozendaal Jenny Hendriks Thierry van Effelterre Bart Spiessens Liesbeth Dekking Laura Solforosi Dominika Czapska-Casey Viki Bockstal Jeroen Stoop Daniel Splinter Sarah Janssen Ben van Baelen Nadia Verbruggen Jan Serroyen Eline Dekeyster Ariane Volkmann Yvonne Wollmann Ricardo Carrion Luis D. Giavedoni Cynthia Robinson Maarten Leyssen Macaya Douoguih Kerstin Luhn Maria Grazia Pau Jerry Sadoff An Vandebosch Hanneke Schuitemaker Roland Zahn Benoit Callendret |
author_sort |
Ramon Roozendaal |
title |
Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate |
title_short |
Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate |
title_full |
Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate |
title_fullStr |
Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate |
title_full_unstemmed |
Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate |
title_sort |
nonhuman primate to human immunobridging to infer the protective effect of an ebola virus vaccine candidate |
publisher |
Nature Publishing Group |
series |
npj Vaccines |
issn |
2059-0105 |
publishDate |
2020-12-01 |
description |
Abstract It has been proven challenging to conduct traditional efficacy trials for Ebola virus (EBOV) vaccines. In the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. We here propose to infer the protective effect of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen with an 8-week interval in humans by immunobridging. Immunogenicity and protective efficacy data were obtained for Ad26.ZEBOV and MVA-BN-Filo vaccine regimens using a fully lethal EBOV Kikwit challenge model in cynomolgus monkeys (nonhuman primates [NHP]). The association between EBOV neutralizing antibodies, glycoprotein (GP)-binding antibodies, and GP-reactive T cells and survival in NHP was assessed by logistic regression analysis. Binding antibodies against the EBOV surface GP were identified as the immune parameter with the strongest correlation to survival post EBOV challenge, and used to infer the predicted protective effect of the vaccine in humans using published data from phase I studies. The human vaccine-elicited EBOV GP-binding antibody levels are in a range associated with significant protection against mortality in NHP. Based on this immunobridging analysis, the EBOV GP-specific-binding antibody levels elicited by the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in humans will likely provide protection against EBOV disease. |
url |
https://doi.org/10.1038/s41541-020-00261-9 |
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