ALEXANDRE, Marie; MARLIN, Romain; PRAGUE, Melanie; COLEON, Severin; KAHLAOUI, Nidhal; CARDINAUD, Sylvain; NANINCK, Thibaut; DELACHE, Benoit; SURENAUD, Mathieu; GALHAUT, Mathilde; DEREUDDRE-BOSQUET, Nathalie; CAVARELLI, Mariangela; MAISONNASSE, Pauline; CENTLIVRE, Mireille; LACABARATZ, Christine; WIEDEMANN, Aurelie; ZURAWSKI, Sandra; ZURAWSKI, Gerard; SCHWARTZ, Olivier; SANDERS, Rogier W; LE GRAND, Roger; LEVY, Yves; THIEBAUT, Rodolphe

doi:10.7554/eLife.75427

Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]

MARLIN, Romain

PRAGUE, Melanie

Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]

Langue

Article de revue

Ce document a été publié dans

eLife. 2022-07-08, vol. 11, p. e75427

Résumé en anglais

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.< Réduire

Mots clés

Graw

Frederik

Davenport

Miles P

Mots clés en anglais

correlate of protection

neutralization

SARS-CoV-2

vaccines

URI

https://oskar-bordeaux.fr/handle/20.500.12278/172172

DOI

http://dx.doi.org/10.7554/eLife.75427

Project ANR

Initiative for the creation of a Vaccine Research Institute
Infrastructure nationale pour la modélisation des maladies infectieuses humaines

Unités de recherche

Bordeaux Population Health Research Center (BPH) - UMR 1219

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Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection