SARS-CoV-2 mechanistic correlates of protection: insight from modelling response to vaccines

Marie Alexandre (1) , Romain Marlin (2) , Mélanie Prague (1) , Séverin Coleon (3, 4) , Nidhal Kahlaoui (2) , Sylvain Cardinaud (3, 4) , Thibaut Naninck (2) , Benoit Delache (2) , Mathieu Surenaud (3, 4) , Mathilde Galhaut (2) , Nathalie Dereuddre-Bosquet (2) , Mariangela Cavarelli (2) , Pauline Maisonnasse (2) , Mireille Centlivre (3, 4) , Christine Lacabaratz (3, 4) , Aurelie Wiedemann (3, 4) , Sandra Zurawski (5) , Gerard Zurawski (5) , Olivier Schwartz (3, 6) , Rogier W Sanders (7) , Roger Le Grand (2) , Yves Levy (3, 4, 8) , Rodolphe Thiébaut (1)

1 SISTM - Statistics In System biology and Translational Medicine
2 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
3 VRI - Vaccine Research Institute [Créteil, France]
4 U955 Inserm - UPEC - IMRB - "From pathophysiology towards immune-basedinterventions in HIV infection" [Créteil]
5 Baylor Scott and White Research Institute and INSERM U955; Dallas, Texas, United States of America
6 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
7 Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute; 1105 AZ Amsterdam, the Netherlands
8 Service d'immunologie clinique et maladies infectieuses [Hôpitaux universitaires CHU Henri Mondor]

The definition of correlates of protection is critical for the development of next generation SARS-CoV-2 vaccine platforms. Here, we propose a new framework 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.

Mots clés: SARS-CoV-2; Correlate of protection; Neutralization; Vaccines

Domaines: Immunologie; Maladies infectieuses; Systèmes dynamiques [math.DS]; Statistiques [math.ST]

Marie Alexandre, Romain Marlin, Mélanie Prague, Séverin Coleon, Nidhal Kahlaoui, et al.. SARS-CoV-2 mechanistic correlates of protection: insight from modelling response to vaccines. 2021. ⟨hal-03482728v1⟩