Non-human primate to human immunobridging demonstrates a protective effect of Ad26.ZEBOV, MVA-BN-Filo vaccine against Ebola

npj Vaccines, vol. 7, pp. 156

Abstract

Without clinical efficacy data, vaccine protective effect may be extrapolated from animals to humans using an immunologic marker that correlates with protection in animals. This immunobridging approach was used for the two-dose Ebola vaccine regimen Ad26.ZEBOV, MVA-BN-Filo. Ebola virus (EBOV) glycoprotein binding antibody data obtained from 764 vaccinated healthy adults in five clinical studies (NCT02416453, NCT02564523, NCT02509494, NCT02543567, NCT02543268) were used to calculate mean predicted survival probability (with preplanned 95% confidence interval [CI]). We used a logistic regression model based on EBOV glycoprotein binding antibody responses in vaccinated non-human primates (NHPs) and NHP survival after EBOV challenge. While the protective effect of the vaccine regimen in humans can be inferred in this fashion, the extrapolated survival probability cannot be directly translated into vaccine efficacy. The primary immunobridging analysis evaluated the lower limit of the CI against predefined success criterion of 20% and passed with mean predicted survival probability of 53.4% (95% CI: 36.7-67.4).

Authors 18

1. Viki Bockstal Aachen Janssen Vaccines & Prevention B.V

   Janssen (Netherlands)

   Affiliation as printed

   ExeVir, Ghent, Belgium

   Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

2. Maarten Leyssen Aachen Janssen Vaccines & Prevention B.V

   Janssen (Netherlands) · KU Leuven

   Affiliation as printed

   Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

   University of Leuven, Leuven, Belgium

3. Dirk Heerwegh

   Janssen (Belgium)

   Affiliation as printed

   Janssen Research and Development, Beerse, Belgium

4. Bart Spiessens

   Janssen (Belgium)

   Affiliation as printed

   Janssen Research and Development, Beerse, Belgium

5. Cynthia Robinson Aachen Janssen Vaccines & Prevention B.V

   Janssen (Netherlands)

   Affiliation as printed

   Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

6. Jeroen N. Stoop Aachen Janssen Vaccines & Prevention B.V

   Janssen (Netherlands)

   Affiliation as printed

   Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

7. Ramon Roozendaal Aachen Janssen Vaccines & Prevention B.V

   Janssen (Netherlands)

   Affiliation as printed

   Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

8. Thierry Van Effelterre

   Janssen (Belgium)

   Affiliation as printed

   Janssen Research and Development, Beerse, Belgium

9. Auguste Gaddah

   Janssen (Belgium)

   Affiliation as printed

   Janssen Research and Development, Beerse, Belgium

10. Griet A. Van Roey Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

11. Laura Solforosi Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

12. Roland C. Zahn Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

13. Benoît Callendret Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

14. Jenny Hendriks Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

15. Kerstin Lühn corresponding Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands. kluhn@its.jnj.com

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

16. Macaya Douoguih Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

17. Hanneke Schuitemaker Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands

18. Johan Van Hoof Aachen Janssen Vaccines & Prevention B.V

    Janssen (Netherlands)

    Affiliation as printed

    Janssen Vaccines & Prevention B.V., Leiden, The Netherlands