A Mathematical Theory of Transmissible Vaccines

每年，数以百万计的人受到野生或野生动植物外溢的病原体的伤害或死亡

Each year, millions of people are harmed or killed by pathogens that spill over from wild or domestic animal reservoirs. A new approach to reducing the threat of spillover is to eliminate the pathogen from its animal reservoir using transmissible vaccines that move from animal to animal providing immunity to the pathogen as they go. Transmissible vaccines reduce the vaccination effort required for pathogen control within animal reservoirs and allow the vaccine to penetrate remote reservoir habitats where direct vaccination is impossible. Bringing this revolutionary idea to fruition requires that we engineer vaccines that simultaneously: 1) transmit efficiently from animal to animal, 2) stimulate a robust immune response to the target pathogen, and 3) maintain their integrity in the face of evolutionary pressures. This project will develop mathematical models that predict how these traits of the vaccine emerge from the interplay between vaccine replication and the animal’s immune response. These models will be parameterized and validated using laboratory studies of prototype transmissible vaccines that use murine cytomegalovirus (MCMV) as a vector backbone. We focus on MCMV as a vector because it is highly species specific, capable of superinfection, and provides a model for vaccine development across murine rodents that serve as important reservoirs for a wide range of human pathogens. The models will be validated using experiments with immune depleted mice that challenge their ability to explain both pattern and process. Work on this project capitalizes on an existing collaboration between experts in mathematical modeling, viral evolution, and murine cytomegalovirus.