Viral dynamics of the Respiratory Syncytial Virus during experimental human challenge: insights for transmission and protection.

Abstract

Respiratory syncytial virus (RSV) is a leading cause of respiratory infection. An in-depth quantification of its clinical, viral, and immune kinetics could provide further insights into tailoring interventions strategies at the individual and population levels. We analyzed high-resolution viral, immunological and clinical data from 225 adults experimentally infected by RSV with mathematical models developed to characterize RSV host-pathogen interaction. The model providing the best fit to the data assumed three main mechanisms of action: a power-law relationship linking viral RNA to infectious virus, an innate immune response that protects target cells and reduces viral production, and an adaptive immune response integrating antibody-mediated and non-antibody-mediated components. The non-antibody-mediated response increased progressively the loss rate of infected cells by about 7-fold (90% Prediction Interval, PI: 2-20), whereas removal of the antibody-mediated response delayed infectious virus clearance by approximately 3.5 days. Infectious virus was detected 3 days post-exposure (dpe) (90% PI: 2-5 dpe), and cleared by 8 dpe (90% PI: 6-11 dpe), defining a median window of detectable infectious virus shedding of approximately 5 dpe (90% PI: 3.5-10 dpe). In contrast, viral RNA persisted longer, with a median clearance time of 12 days (90% PI: 9-15 dpe). Finally, the analysis of clinical evolution showed a significant association between the occurrence of symptoms and viral dynamics. While pauci-symptomatic individuals represented 35% of our population, they accounted for only ∼ 5% of infectious viral shedding. These results provide new insights into RSV infection to inform diagnostics, isolation and prevention strategies.