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J Theor Biol. 2020 Mar 20:110254. doi: 10.1016/j.jtbi.2020.110254. [Epub ahead of print]

A model for establishment, maintenance and reactivation of the immune response after vaccination against Ebola virus.

Author information

1
INSERM U1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France; INRIA SISTM team, Talence, France; Vaccine Research Institute, Créteil, France. Electronic address: irene.balelli@u-bordeaux.fr.
2
INSERM U1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France; INRIA SISTM team, Talence, France; Vaccine Research Institute, Créteil, France; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. Electronic address: cgp2121@cumc.columbia.edu.
3
INSERM U1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France; INRIA SISTM team, Talence, France; Vaccine Research Institute, Créteil, France. Electronic address: melanie.prague@u-bordeaux.fr.
4
Université de Bordeaux, CNRS, Bordeaux INP, IMB, UMR 5251, F-33400 Talence, France. Electronic address: fabien.crauste@u-bordeaux.fr.
5
Janssen Pharmaceutica N.V., Beerse, Belgium. Electronic address: tvaneffe@ITS.JNJ.com.
6
Janssen Vaccines & Prevention B.V., Leiden, The Netherlands. Electronic address: vbocksta@its.jnj.com.
7
Janssen Vaccines & Prevention B.V., Leiden, The Netherlands. Electronic address: lsolforo@its.jnj.com.
8
INSERM U1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France; INRIA SISTM team, Talence, France; Vaccine Research Institute, Créteil, France. Electronic address: rodolphe.thiebaut@u-bordeaux.fr.

Abstract

The 2014-2016 Ebola outbreak in West Africa has triggered accelerated development of several preventive vaccines against Ebola virus. Under the EBOVAC1 consortium, three phase I studies were carried out to assess safety and immunogenicity of a two-dose heterologous vaccination regimen developed by Janssen Vaccines and Prevention in collaboration with Bavarian Nordic. To describe the immune responses induced by the two-dose heterologous vaccine regimen, we propose a mechanistic ODE based model, which takes into account the role of immunological memory. We perform identifiability and sensitivity analysis of the proposed model to establish which kind of biological data are ideally needed in order to accurately estimate parameters, and additionally, which of those are non-identifiable based on the available data. Antibody concentrations data from phase I studies have been used to calibrate the model and show its ability in reproducing the observed antibody dynamics. Together with other factors, the establishment of an effective and reactive immunological memory is of pivotal importance for several prophylactic vaccines. We show that introducing a memory compartment in our calibrated model allows to evaluate the magnitude of the immune response induced by a booster dose and its long-term persistence afterwards.

KEYWORDS:

Calibration; Ebola Virus; Heterologous vaccination; Identifiability analysis; Immunological memory; Mechanistic modeling; Sensitivity analysis; Vaccination

PMID:
32205143
DOI:
10.1016/j.jtbi.2020.110254

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