A Mathematical Theory of Transmissible Vaccines

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: SCOTT L NUISMER
Organization: UNIVERSITY OF IDAHO
Fiscal Year: 2024
Award: $335,075
Funding agency: National Institute of General Medical Sciences

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.

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