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Rutgers New Jersey Medical School Scientists Study How Worm Infections Can Weaken Immune Systems — And Life-Saving Vaccinations

8/11/2017

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New Brunswick, NJ — Why are malaria, tuberculosis and hepatitis so prevalent in developing nations?  And why are most vaccines against these pathogens so ineffective?
 
Two Rutgers New Jersey Medical School scientists believe they may have found an answer in parasitic intestinal worms — which infect more than 1.5 billion people worldwide and can weaken the immune system’s ability to fend off disease, rendering vaccines less effective. 
 
George Yap and William Gause received a $3 million grant from the National Institutes of Health this spring to study how worms prevent vaccinations from bolstering the immune system.
 
Their results could aid in the fight against diseases including malaria and tuberculosis, which kill more than 1 million and 1.8 million each year respectively, according to the World Health Organization.
​“We want to find out how to make vaccines effective even if someone has a worm infection,” said Yap, an associate professor with the Center for Immunity and Inflammation whose research focuses on the development of CD8 cells. “It could save millions of lives and resource dollars.”
 
The pair previously found that worm infections weaken the immune system’s fighter cells — also called CD8 cells. Yap and Gause will spend the next five years studying CD8 cells in worm-infected mice trying to pinpoint exactly how secretions produced by worms impair those fighter cells.
 
“Worms’ capacity to regulate the human immune response never ceases to amaze me,” said Gause, professor of medicine at NJMS and senior associate dean for research and director of the RHS Institute for Infectious and Inflammatory Diseases.
 
“When they travel through tissues in the body, they damage the tissues and the tissues themselves release danger signals that can trigger immune responses,” Gause said.
 
The hope is that understanding how fighter cells are weakened by worms will lead to the development of vaccines that can circumvent this response and remain effective in non-industrialized nations where worm infections are rampant.
 
Why do doctors not just treat worms — also known as helminth — instead?
 
Parasitic worms — coevolving with vertebrates for 400 million years — are among the world’s most common infections and affect the most deprived communities. They are spread by eggs in human feces which contaminate soil in areas with poor sanitation.
 
“Helminths are quite difficult to get rid of in parts of the world,” said Gause. “You can give a person an anti-helminth drug, but they go back to their village and get re-infected again.”
 
Over treating populations for worm infections may lead to the development of drug-resistant strains, said Gause, who has been researching helminths and their impact on the human immune system since 1985 and is conducting a tandem study  on the parasite with another NJMS peer, George Hasko.
 
This second five-year, $3.2 million study, also awarded by the NIH, will examine how the immune system actually detects the worm infection, and then becomes activated to protect against the parasite while weakening the very immune components that protect us against microbes, like tuberculosis. 
 
When combined, the results of both NIH funded studies will help guide scientists working to help those living with too many worms — as well as those living with too few.
 
“That is the double-edged sword of the immune response we’ve developed while co-evolving with worms,” said Gause. “One hypothesis is we are living in too hygienic a world, so the immune system doesn’t develop normally.”
 
Scientists, including Gause and Yap, theorize that without worms to attack, the immune system attacks itself, leading to a rise in immune disorders like allergies, diabetes and IBD (inflammatory bowel disease).
 
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