Dr. Joseph Malinzi
Uganda Martyrs University, Uganda
Talk is at 11:00 AM Central Time (calculating your local time…)
Abstract
I will present a mathematical model of synergistic oncolytic virotherapy combining Vesicular Stomatitis Virus (VSV) and Vaccinia Virus (VV). The model centres on the B18R protein secreted by VV-infected cells, which neutralises interferon-α (IFN-α) and potentiates VSV replication, creating a dynamic ping-pong oncolytic effect between the two viruses. Simulations show that combination therapy clears tumours substantially faster than either monotherapy. Bifurcation analysis identifies critical thresholds in burst size and B18R inhibition efficiency, while sensitivity analysis highlights infection rates and burst sizes as the key therapeutic levers. Temporal optimisation establishes that efficacy is maximised when VV follows VSV by 5–19 hours, or VSV follows VV by 14–24 hours.
I will also introduce an extended model in which a recombinant VSV additionally expresses the FAST protein, promoting tumour cell-cell fusion and syncytia formation. This introduces a dual-pivot mechanism: B18R-mediated immune evasion enhances VSV oncolysis, while FAST expression promotes VV spread via syncytia formation, creating a second, complementary pathway for viral dissemination. The model is formulated and its mathematical structure established; full analysis is ongoing.
Joint work with Raluca Eftimie, Anotida Madzvamuse and Helen Byrne.
Keywords: oncolytic virotherapy · Vaccinia Virus · Vesicular Stomatitis Virus · viral synergy · FAST protein · syncytia · interferon-α · optimal control · mathematical oncology