Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection.
Elife
; 112022 07 08.
Article
en En
| MEDLINE
| ID: mdl-35801637
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
SARS-CoV-2
/
COVID-19
Límite:
Animals
/
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article