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

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...

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Autores principales: Alexandre, Marie, Marlin, Romain, Prague, Mélanie, Coleon, Severin, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282856/
https://www.ncbi.nlm.nih.gov/pubmed/35801637
http://dx.doi.org/10.7554/eLife.75427
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author Alexandre, Marie
Marlin, Romain
Prague, Mélanie
Coleon, Severin
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
author_facet Alexandre, Marie
Marlin, Romain
Prague, Mélanie
Coleon, Severin
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
author_sort Alexandre, Marie
collection PubMed
description 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.
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spelling pubmed-92828562022-07-15 Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection Alexandre, Marie Marlin, Romain Prague, Mélanie Coleon, Severin 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 eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2022-07-08 /pmc/articles/PMC9282856/ /pubmed/35801637 http://dx.doi.org/10.7554/eLife.75427 Text en © 2022, Alexandre et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Alexandre, Marie
Marlin, Romain
Prague, Mélanie
Coleon, Severin
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
Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
title Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
title_full Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
title_fullStr Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
title_full_unstemmed Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
title_short Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection
title_sort modelling the response to vaccine in non-human primates to define sars-cov-2 mechanistic correlates of protection
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282856/
https://www.ncbi.nlm.nih.gov/pubmed/35801637
http://dx.doi.org/10.7554/eLife.75427
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