Experimental plague vaccine protects immune-deficient mice
A mouse study found live-attenuated plague vaccines, paired with a viral vector shot, protected against lethal pneumonic plague.
By Priya Raghavan · Science Reporter
3 min read
An experimental plague vaccine approach protected mice from lethal pneumonic plague even when the animals lacked a major immune-signaling protein, researchers reported in Science Translational Medicine. The finding matters because the United States has no FDA-approved plague vaccine, and antibiotic-resistant strains of the bacterium remain a concern, according to the study report.
The work tested two live-attenuated vaccines, called LMA and LMP, made from weakened forms of Yersinia pestis, the bacterium that causes plague. Researchers also tested them with Ad5-YFV, an adenovirus type 5-based vaccine designed to deliver three plague proteins to the immune system.
In mice genetically engineered to lack interferon-gamma, a protein involved in activating immune cells, the vaccine strategies protected 80% to 100% of animals exposed to highly lethal doses of the pneumonic plague strain Yp CO92, according to the researchers. Vaccinated animals also produced strong antibody and cellular immune responses.
How did the plague vaccine protect mice?
The strongest results came from a two-step “prime-pull” schedule: an injection into muscle followed by a nasal spray 21 days later, according to the study. The injection prepared the immune system, while the nasal dose drew immune defenses toward the nose and lungs, where pneumonic plague enters and spreads.
Pneumonic plague is a severe lung infection caused by Yersinia pestis. Unlike bubonic plague, it involves the respiratory system and can be especially dangerous during outbreaks.
The researchers compared ordinary mice with mice missing interferon-gamma and mice lacking three types of immune protein receptors. After vaccination, they analyzed blood and lung fluid to measure immune responses before challenging the animals with plague bacteria.
The vaccines protected mice even when parts of the immune system were absent, according to the study. The animals also withstood a later bacterial exposure described as 10,000 times higher than the normally fatal dose.
The immune patterns varied by mouse group. Normal mice had higher antibody levels in lung fluid and more broad-purpose immune cells, while mice with immune defects showed more memory T cells and stronger activity in tissues where antibodies are made, the researchers reported.
Why researchers are looking for broader plague vaccines
Plague is no longer causing pandemics like those recorded in history, but it still appears in several regions. The study report notes that Madagascar recorded 2,575 plague cases in 2017, with 77% involving pneumonic plague and about 9% of infected people dying; a 2021 outbreak had a reported death rate of 37%.
Many experimental plague vaccines focus on two bacterial proteins, but Y. pestis can change or lose those targets, according to the researchers. In this study, the vaccine combinations protected mice against several naturally occurring plague variants and strains described as able to evade other experimental vaccines.
The researchers said combining a live-attenuated vaccine with an adenovirus-based vaccine increased immune activity both across the body and in the lungs. They framed the approach as a possible path toward longer-lasting protection against pneumonic plague.
The evidence remains limited to mouse models. The researchers said testing in nonhuman primates and then human clinical trials would be needed before the strategy could be assessed for human use.
This story draws on original reporting from Medical Xpress.