The efficacy of antibody-dependent vaccines relies on both virus replication and neutralisation, but their quantitative relationship is unknown. To bridge this gap, we investigated the growth of avian and human influenza viruses, and the virus neutralisation by antibodies in vitro. A one-dimensional deterministic model accurately predicted the growth of avian and human influenza in cell culture, and neutralisation of seasonal influenza viruses determined using focus reduction assay. According to this model, at a specific interval of antibody concentration, viruses can either survive or die due to bistability, where small viral inocula are eliminated but not large virus inocula; this is caused by saturated virus neutralization or antibody consumption. Our finding highlights the importance of inoculum size even when virus-antibody pair is well-matched and provides a possible mechanism for high influenza re-infections and low vaccine efficacy, thereby facilitating the formulation of strategies to enhance the efficacy of influenza vaccines and antiviral treatments.

Saturation of influenza virus neutralization and antibody consumption can both lead to bistable growth kinetics