eLife (Jul 2022)
Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
- Marie Alexandre,
- Romain Marlin,
- Mélanie Prague,
- Severin Coleon,
- Nidhal Kahlaoui,
- Sylvain Cardinaud,
- Thibaut Naninck,
- Benoit Delache,
- Mathieu Surenaud,
- Mathilde Galhaut,
- Nathalie Dereuddre-Bosquet,
- Mariangela Cavarelli,
- Pauline Maisonnasse,
- Mireille Centlivre,
- Christine Lacabaratz,
- Aurelie Wiedemann,
- Sandra Zurawski,
- Gerard Zurawski,
- Olivier Schwartz,
- Rogier W Sanders,
- Roger Le Grand,
- Yves Levy,
- Rodolphe Thiébaut
Affiliations
- Marie Alexandre
- ORCiD
- University of Bordeaux, Department of Public Health, Inserm Bordeaux Population Health Research Centre, Inria SISTM, Bordeaux, France
- Romain Marlin
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Mélanie Prague
- ORCiD
- University of Bordeaux, Department of Public Health, Inserm Bordeaux Population Health Research Centre, Inria SISTM, Bordeaux, France
- Severin Coleon
- Vaccine Research Institute, Créteil, France; Inserm U955, Créteil, France
- Nidhal Kahlaoui
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Sylvain Cardinaud
- Vaccine Research Institute, Créteil, France; Inserm U955, Créteil, France
- Thibaut Naninck
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Benoit Delache
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Mathieu Surenaud
- Vaccine Research Institute, Créteil, France; Inserm U955, Créteil, France
- Mathilde Galhaut
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Nathalie Dereuddre-Bosquet
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Mariangela Cavarelli
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Pauline Maisonnasse
- ORCiD
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Mireille Centlivre
- Vaccine Research Institute, Créteil, France; Inserm U955, Créteil, France
- Christine Lacabaratz
- Vaccine Research Institute, Créteil, France; Inserm U955, Créteil, France
- Aurelie Wiedemann
- Vaccine Research Institute, Créteil, France; Inserm U955, Créteil, France
- Sandra Zurawski
- Baylor Scott and White Research Institute, Dallas, United States
- Gerard Zurawski
- Baylor Scott and White Research Institute, Dallas, United States
- Olivier Schwartz
- ORCiD
- Vaccine Research Institute, Créteil, France; Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR 3569, Paris, France
- Rogier W Sanders
- Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands
- Roger Le Grand
- ORCiD
- Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France
- Yves Levy
- Vaccine Research Institute, Créteil, France; Inserm U955, Créteil, France; AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses, Créteil, France
- Rodolphe Thiébaut
- ORCiD
- University of Bordeaux, Department of Public Health, Inserm Bordeaux Population Health Research Centre, Inria SISTM, Bordeaux, France; Vaccine Research Institute, Créteil, France; CHU Bordeaux, Department of Medical information, Bordeaux, France
- DOI
- https://doi.org/10.7554/eLife.75427
- Journal volume & issue
-
Vol. 11
Abstract
The definition of correlates of protection is critical for the development of next-generation SARS-CoV-2 vaccine platforms. Here, we propose a model-based approach for identifying mechanistic correlates of protection based on mathematical modelling of viral dynamics and data mining of immunological markers. The application to three different studies in non-human primates evaluating SARS-CoV-2 vaccines based on CD40-targeting, two-component spike nanoparticle and mRNA 1273 identifies and quantifies two main mechanisms that are a decrease of rate of cell infection and an increase in clearance of infected cells. Inhibition of RBD binding to ACE2 appears to be a robust mechanistic correlate of protection across the three vaccine platforms although not capturing the whole biological vaccine effect. The model shows that RBD/ACE2 binding inhibition represents a strong mechanism of protection which required significant reduction in blocking potency to effectively compromise the control of viral replication.
Keywords
