The plague has killed more people than World War II. The bacterium Yersinia pestis (Yp), which causes plague, has triggered three major pandemics throughout history, leaving behind a casualty toll of more than 200 million people. Although the plague no longer causes pandemics on the scale seen in history, it still occurs in many parts of the world today. Vaccination remains our best defense against the disease, but approved options remain scarce.

In a new study, scientists tested two live-attenuated plague vaccines, LMA and LMP—weakened forms of the plague bacterium that cannot cause disease—both alone and in combination with the virus-based vaccine Ad5-YFV.

They genetically engineered the mice to completely lack a signaling protein called interferon-gamma, which plays a crucial role in activating immune cells. Despite lacking a key immune protein, the vaccines protected 80% to 100% of mice exposed to highly lethal doses of the pneumonic plague-causing Yp CO92 strain, while triggering strong antibody and immune responses in all vaccinated animals.