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

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: eLife, Vol 11 (2022)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.75427
Popis: 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.
Databáze: Directory of Open Access Journals