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.
Keywords: SARS-CoV-2; correlate of protection; immunology; inflammation; neutralization; rhesus macaque; vaccines; viruses.
【저자키워드】 immunology, SARS-CoV-2, Inflammation, Vaccines, neutralization, Correlate of protection, viruses., rhesus macaque, 【초록키워드】 viruses, ACE2, Vaccine, Infection, inhibition, SARS-CoV-2 vaccine, viral replication, mRNA, Mathematical modelling, viral dynamics, vaccine platform, non-human primate, Critical, mechanism, binding, infected cells, RBD binding, rhesus, clearance, approach, immunological, Cell, decrease, robust, identify, required, appear, increase in, reduction in, main mechanism, 【제목키워드】 Vaccine, non-human primate, to define,