Researchers at the University of Texas Medical Branch in Galveston have developed experimental vaccine strategies that protected mice against pneumonic plague, one of the deadliest forms of the disease, even when the animals lacked an immune system protein long thought essential for fighting bacterial infections.
The study, published in Science Translational Medicine, challenges decades of assumptions about how the body defends itself against plague and could shape the design of future vaccines.
Plague remains a modern threat
Pneumonic plague is a fast-moving, severe lung infection caused by the bacterium Yersinia pestis, the same pathogen behind the Black Death. The disease is rare in the modern world, but it has not disappeared. Cases still occur in parts of Africa, Asia and the Americas, including occasional cases in the United States. The Centers for Disease Control and Prevention reports an average of seven U.S. cases annually in recent decades.
The World Health Organization classifies Y. pestis as a priority pathogen, citing its epidemic and pandemic potential. Researchers also remain concerned about antibiotic-resistant strains.
No plague vaccine currently has approval from the U.S. Food and Drug Administration.
Protection without interferon-gamma
“Our findings show these vaccines generate a remarkably broad immune response,” said Dr. Ashok Chopra, a professor and John S. Dunn Distinguished Chair in Global Health in UTMB’s Department of Microbiology and Immunology, who led the research. “Even without interferon-gamma, which has long been considered one of the immune system’s most important antibacterial defenses, vaccinated animals remained protected from lethal pneumonic plague.”
That last part is the twist at the center of the study.
Interferon-gamma is a signaling protein that helps different parts of the immune system coordinate their attack on bacteria. Researchers have generally treated it as essential for surviving plague infection.
To test that assumption, the UTMB team vaccinated two groups of mice: normal mice and mice genetically engineered to lack interferon-gamma. The researchers evaluated two live attenuated plague vaccines developed at UTMB, both individually and in combination with a separate adenovirus-based vaccine carrying three plague antigens.
Researchers then exposed the mice to Y. pestis. Nearly all vaccinated mice survived, including those without interferon-gamma. In a separate experiment, researchers temporarily blocked interferon-gamma in vaccinated normal mice immediately before infection, and the vaccines continued to provide complete protection.
“The immune system has multiple ways to recognize and fight infection,” said Dr. Emily Hendrix, the study’s first author, who worked on the project as a doctoral student and postdoctoral fellow and now continues her research at Seattle Children’s Hospital. “These vaccines appear to activate several of those pathways at once, producing strong antibody responses, long-lasting immune memory, and protective immunity in the lungs, where pneumonic plague attacks.”
Vaccines protect against multiple strains
The researchers also tested the vaccines against several strains of Y. pestis, including strains lacking one of the bacterial proteins targeted by earlier vaccine approaches. The vaccines protected against those strains, too, suggesting the approach could work against naturally occurring variation and potential engineered variants.
The combination strategy produced particularly strong immune responses in lung tissue, an important finding because pneumonic plague spreads rapidly through the respiratory system.
Pneumonic plague can develop when bacteria reach the lungs through inhalation or spread from another form of the disease. Without treatment, it can become fatal within 18 to 24 hours of symptoms beginning. A vaccine combination that triggers strong immune activity in the respiratory tract would target the disease where it causes the most damage.
Human testing remains ahead
UTMB researchers caution that the work remains in the early, preclinical stage. Mice are not people, and a vaccine that succeeds in animal studies still faces additional research before scientists can test it in humans.
But for a disease linked to one of history’s deadliest pandemics and still lacking an FDA-approved vaccine, protection without interferon-gamma gives scientists a new line of inquiry.
Provided by Dallas Express
