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Finding Cholera's Weak Spot Could Advance Vaccine Design

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Findings from a team led by investigators at Massachusetts General Hospital (MGH), reported in the online journal mBio, may help scientists develop a more effective vaccine for cholera, a bacterial disease that causes severe diarrhea and dehydration and is usually spread through contaminated water.

The bacterium that causes cholera, called Vibrio cholerae, settles within the intestines after ingestion. There, it secretes a toxin that causes intestinal cells to secrete massive amounts of fluid, eventually leading to death from dehydration and shock if untreated. The disease is a significant problem in many impoverished regions of the world.

Interestingly, immune responses to the toxin do not protect against cholera, but previous research led by investigator Edward Ryan, MD, director of Global Infectious Diseases at MGH,  has shown  antibodies that bind V. cholerae’s sugar coating—called O-specific polysaccharide (OSP)—do offer protection.

“A big question is: How do these antibodies protect? The answer would help develop better vaccines,” says  Ryan, who is also a professor of Medicine at Harvard Medical School and a professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health. He notes current vaccines for cholera are not very protective in young children, who bear much of the global burden of cholera, and induce relatively short-term protection in recipients.  

To investigate, Ryan and his colleagues analyzed antibodies recovered from humans who survived cholera. Experiments showed  the antibodies block V. cholerae bacteria’s motility. “V. cholerae are very mobile, and swimming is critical to their ability to cause disease,” Ryan explains. “Interestingly, the tail-like flagellum in V. cholerae that propels swimming is coated with the OSP sugar.” More detailed analyses demonstrated  the human antibodies attached to this OSP coating to block the ability of V. cholerae to swim and cause disease.

“Our results support a unique mechanism of protection against a human pathogen. We are not aware of previous work demonstrating a comparable direct anti-motility effect of human antibodies,” says Ryan.

Charles RC, Kelly M, Tam JM, et al. Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility. mBio. 2020;11(6). doi:10.1128/mBio.02847-20

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