Background: Respiratory syncytial virus (RSV) is a common respiratory virus that can cause serious illness in infants and the elderly. Vaccines for RSV have recently been introduced and have been shown to reduce the severity of the disease. However, there has been limited examination of how viral dynamics differ between vaccinated and unvaccinated individuals. Methods: Here, we use data from the MVA-BN-RSV Phase II vaccine study to quantify the dynamical differences between vaccinated and unvaccinated patients challenged with RSV. We use an ordinary differential equation model of within host viral dynamics to fit viral load data. Results: We find statistically significant differences in viral clearance rate and basic reproduction number. We also find that vaccinated patients experience a higher response variance than the placebo group. Conclusions: While the differences in viral clearance and basic reproduction number are promising, the high variability in response to the vaccine could leave many vaccinated patients without adequate protection.

Highly pathogenic avian influenza viruses, such as H5N1, cause severe disease in humans and pose a persistent pandemic threat, yet the mechanism by which the type I interferon response shapes their within-host dynamics remains unclear. Here we fit three ordinary differential equation models, in which interferon reduces the viral infection rate, reduces viral production, or drives cells into a refractory state, to paired viral load and IFN-\(\alpha \)2 time courses from human nasal and tracheal respiratory epithelium infected with a seasonal H3N2 strain and with 2005 and 2022 clades of H5N1. Although the refractory-state model attains the lowest residual error in most conditions, the small-sample-corrected Akaike information criterion does not justify its additional parameter, and the two alternative mechanisms, reduction of infection rate or reduction of production rate, describe the data comparably well. While a structural identifiability analysis suggests all parameters are globally identifiable when both viral titer and interferon are observed, with only ten observations per condition the data cannot single out one mechanism of interferon action. The bootstrapped parameter distributions are largely similar across strains when compared with a Mann-Whitney U-test, differing mainly in the rate of interferon clearance, with only modest differences between the nasal and tracheal epithelium. These results quantify the interferon response to avian influenza in human respiratory tissue and underscore the need for more frequently sampled data to resolve the dominant mechanism of interferon action in vivo.

A bstract: Oncolytic vaccinia viruses (OVVs) present a promising approach for melanoma treatment due to their ability to selectively infect and lyse tumor cells. In this study, we use an ordinary differential equation (ODE) model of tumor growth inhibited by OVV activity to parameterize previous research on the effect of neutrophil depletion in B16-F10 melanoma tumors in mice. We find that the data are best fit by a model that accounts for neutrophil-mediated viral clearance, and that neutrophil depletion provides a mechanism for enhanced OVV efficacy and tumor reduction. We also find that parameter estimates for the most effective OVV regime share characteristics, most notably a low viral clearance rate by neutrophils, that might explain the improved outcomes. Further studies examining the impact of neutrophil modulation across different tumor models may help elucidate the extent to which these findings generalize and inform the design of novel OVV-based cancer therapies.