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- Title
Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection.
- Authors
Alexandre, Marie; Marlin, Romain; Prague, Mélanie; 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.
- 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.
- Subjects
VACCINE effectiveness; COVID-19 vaccines; PRIMATES; SARS-CoV-2; DATA mining
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.75427