| Literature DB >> 35801637 |
Romain Marlin1, Mélanie Prague2, Marie Alexandre2, Severin Coleon3,4, Nidhal Kahlaoui1, Sylvain Cardinaud3,4, Thibaut Naninck1, Benoit Delache1, Mathieu Surenaud3,4, Mathilde Galhaut1, Nathalie Dereuddre-Bosquet1, Mariangela Cavarelli1, Pauline Maisonnasse1, Mireille Centlivre3,4, Christine Lacabaratz3,4, Aurelie Wiedemann3,4, Sandra Zurawski5, Gerard Zurawski5, Olivier Schwartz3,6,7, Rogier W Sanders8, Roger Le Grand1, Yves Levy3,4,9, Rodolphe Thiébaut2,3,10.
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.Entities:
Keywords: SARS-CoV-2; correlate of protection; immunology; inflammation; neutralization; rhesus macaque; vaccines; viruses
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Year: 2022 PMID： 35801637 PMCID： PMC9282856 DOI： 10.7554/eLife.75427
Source DB: PubMed Journal: Elife ISSN： 2050-084X Impact factor: 8.713