Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
- University of Bordeaux, Inria SISTM, UMR 1219, France
- Université Paris-Saclay, Inserm, CEA, France
- Vaccine Research Institute, Inserm U955, France
- Baylor Scott and White Research Institute, United States
- Institut Pasteur, France
- University of Amsterdam, Netherlands
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.
Data availability
No unique reagents were generated for this study.Data that support the findings of this study are provided in the source data files of this paper and gather data from 1) the study [Marlin, Nature Com 2021] used in this analysis, which are also directly available online in the section Source data of this related paper (https://www.nature.com/articles/s41467-021-25382-0#Sec17) ; 2) the study [Brouwer, Cell 2021] used in this analysis, which are also available from the corresponding authors of the related paper and 3) the study [Corbett, NEJM 2020] used in this analysis, which are also available online in the section Supplementary Material of the related paper, excel file labelled ("Supplementary Appendix 2"). Data from the main study [Marlin, Nature Com 2021] can also be found in the open-access repository Dryad using the following DOI: https://doi.org/10.5061/dryad.1zcrjdfv7.The original code (mlxtran models and R) as well as model definition files including the full list of parameters used are available and free-of-cost on github (Inria SISTM Team) at the following link: https://github.com/sistm/SARSCoV2modelingNHP.
Article and author information
Author details
Pauline Maisonnasse
Funding
Agence Nationale de la Recherche (ANR-10-LABX-77-01)
- Yves Levy
- Rodolphe Thiébaut
Agence Nationale de la Recherche (ANR-11- 1018 INBS-0008)
- Roger Le Grand
This work was supported by INSERM and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR under reference ANR-10-LABX-77-01. MA has been funded by INRIA PhD grant. The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the Programme Investissements d'Avenir"
Ethics
Animal experimentation: Cynomolgus macaques (Macaca fascicularis), aged 37-66 months (18 females and 13 males) and originating from Mauritian AAALAC certified breeding centers were used in this study. All animals were housed in IDMIT facilities (CEA, Fontenay-aux-roses), under BSL2 and BSL-3 containment when necessary (Animal facility authorization #D92-032-02, Préfecture des Hauts de Seine, France) and in compliance with European Directive 2010/63/EU, the French regulations and the Standards for Human Care and Use of Laboratory Animals, of the Office for Laboratory Animal Welfare (OLAW, assurance number #A5826-01, US). The protocols were approved by the institutional ethical committee "Comité d'Ethique en Expérimentation Animale du Commissariat à l'Energie Atomique et aux Energies Alternatives" (CEtEA #44) under statement number A20-011. The study was authorized by the "Research, Innovation and Education Ministry" under registration number APAFIS#24434-2020030216532863v1.
Copyright
© 2022, Alexandre et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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