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

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Alexandre, Marie | Marlin, Romain | Prague, Mélanie | Coleon, Séverin | 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 | Thiébaut, Rodolphe

Edité par CCSD ; eLife Sciences Publication -

International audience. 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.

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