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

• DOI: 10.7554/elife.75427
• Publication Date: 2022-07-08T10:00:23Z
• Authors: Marie Alexandre; Romain Marlin; Mélanie Prague; Severin Coleon; Nidhal Kahlaoui; Sylvain Cardinaud; Thibaut Naninck; Benoit Delache; Mathieu Surenaud; Mathilde Galhaut; Nathalie Dereuddr...; 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
• Keywords: Primates; 0301 basic medicine; COVID-19 Vaccines; QH301-705.5; [SDV]Life Sciences [q-bio]; Science; [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS]; Funding acquisition; Supervision; Antibodies, Viral; 03 medical and health sciences; Neutralization; Immunology and Inflammation; [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST]; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; Validation; Animals; Humans; correlate of protection; Biology (General); Vaccines; Writing - Conceptualization; SARS-CoV-2; Q; Methodology; R; Correlate of protection; COVID-19; neutralization; vaccines; Antibodies, Neutralizing; Resources; 3. Good health; Writing -original draft; Writing -; Spike Glycoprotein, Coronavirus; [SDV.IMM]Life Sciences [q-bio]/Immunology; Medicine; Project administration Resources Supervision Writing -original draft Writing - Conceptualization Funding acquisition Methodology Project administration Supervision Validation Writing -; Angiotensin-Converting Enzyme 2; Project administration

The definition of correlates protection is critical for the development next-generation SARS-CoV-2 vaccine platforms. Here, we propose a model-based approach identifying mechanistic based on mathematical modelling viral dynamics and data mining immunological markers. application to three different studies in non-human primates evaluating vaccines CD40-targeting, two-component spike nanoparticle mRNA 1273 identifies quantifies two main mechanisms that are decrease rate cell infection an increase clearance infected cells. Inhibition RBD binding ACE2 appears be robust correlate across platforms although not capturing whole biological effect. model shows RBD/ACE2 inhibition represents strong mechanism which required significant reduction blocking potency effectively compromise control replication.