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Infectious diseases continue to be a leading cause of sickness and death in livestock and are of concern to human health due to their potential to be transferred to people. Vaccination is the most cost-effective means of preventing infectious disease in animals and humans, but its application to livestock is still limited, and the lack of effective vaccines contributes to the excessive use of antibiotics in animal health. This project aims to use ‘reverse vaccinology’ to develop vaccines for Johne’s disease and bovine tuberculosis in cattle. These diseases result in annual losses of more than $86 million and $10 million, respectively, in Canada and billions annually worldwide. The major deliverables of this project will be two new vaccines for the above diseases influencing the food and dairy industries, companion diagnostics that will differentiate vaccinated from infected animals, and a white paper to inform the public, producers, industry and government on the options and strategies for dealing with these important cattle diseases. The vaccines developed through this project will benefit dairy and beef cattle farmers, the public who utilize their products and the commercial sector, both in terms of marketable vaccines, increased food and dairy product output, and international trade.