(342aa) Mathematical Modeling of the Observed Neutralization Threshold of Antibodies Against Sars-Cov-2

Neutralizing antibodies for SARS-CoV-2 commonly bind to the receptor binding domain (RBD) on the surface of the trimeric viral fusion Spike (S) protein, to prevent the virus from attaching to its cellular target angiotensin-converting enzyme 2 (ACE2) to gain entry into human cells. Neutralization assays show there is a strict neutralization threshold for SARS-CoV-2 virus particles at 0.001 μm/mL of antibody. To examine this phenomenon, a mathematical model incorporating the association and dissociation rates of RBD-targeting antibodies was developed. The number of bound antibodies was then translated into a corresponding degree of viral infectivity. Our model shows that at a concentration of 0.001 μm/mL of antibody, despite a sufficient number of antibodies available to bind to the virus, the antibodies are unable to fully neutralize the virus. Therefore, the dynamics of binding, governed by the association and dissociation of the antibodies from the S protein, results in the strict neutralization cutoff observed in the experiments. An overarching finding of this work is that neutralization thresholds for multiple viruses can be predicted using such a mathematical model that describes viral infectivity as it relates to the number of bound antibodies. For example, this model can also be employed to understand the origins of the antibody neutralization threshold against human immunodeficiency virus (HIV), where it is also observed. A more general understanding of the specific antibody concentrations at which neutralization thresholds occur for different diseases could guide the design of future vaccines against these and other diseases.