Non-human primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate
| Autor: | Bart Spiessens, Ramon Roozendaal, Liesbeth Dekking, Maria Grazia Pau, Cynthia Robinson, Dominika N. Czapska-Casey, Yvonne Wollmann, Thierry Van Effelterre, Viki Bockstal, Eline Dekeyster, Roland Zahn, Jeroen N Stoop, Kerstin Luhn, Jan Serroyen, Luis D. Giavedoni, Jenny Hendriks, Sarah Janssen, Maarten Leyssen, Ben Van Baelen, Hanneke Schuitemaker, Ricardo Carrion, Daniel Splinter, An Vandebosch, Jerry Sadoff, Ariane Volkmann, Nadia Verbruggen, Macaya Douoguih, Laura Solforosi, Benoit Callendret |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology Disease medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Immune system Vaccine Immunogenicity Medicine Pharmacology (medical) 030212 general & internal medicine RC254-282 Pharmacology Vaccines Ebola virus biology business.industry Immunogenicity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC581-607 Virology Nonhuman primate 3. Good health Regimen 030104 developmental biology Infectious Diseases biology.protein Immunologic diseases. Allergy Antibody business |
| Zdroj: | NPJ VACCINES npj Vaccines NPJ Vaccines npj Vaccines, Vol 5, Iss 1, Pp 1-11 (2020) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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