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Published On February 3, 2021

DISCOVERIES OF 2020

A Better Cholera Vaccine?

Puzzling through the cholera antibody response may help slow a disease that affects millions of people every year.

The COVID-19 pandemic brought a vast mobilization of scientific ingenuity. At the same time, work on other medical threats continued to push forward. This week, Proto looks at the most transformational non-COVID-19 research of 2020.

After a quarter century studying cholera in Bangladesh, Edward Ryan, director of Global Infectious Diseases at Massachusetts General Hospital, and his team have solved one of the disease’s remaining riddles. The discovery, published in November in the journal mBio, offers a promising target for a vaccine that may finally prevent young children from dying of cholera.

Endemic to 51 countries, cholera sickens 3 million people and kills another 95,000 each year. While a vaccine currently exists, it is only partly effective for reasons that had not been well understood. “The existing cholera vaccine is about 65% effective,” says Ryan. “Immunity lasts only for a few years, and the vaccine doesn’t protect children under the age of five.”

Individuals who survive cholera have about a 10-year window of protection against getting severely ill from cholera again. “We know that people develop antibodies against the cholera toxin, but interestingly these antibodies do not protect them against the disease,” says Ryan. “So what antibodies are protective?”

After people ingest the organism from contaminated water, Vibrio cholerae swims within the intestines and secretes the toxin that causes voluminous watery diarrhea, which can eventually lead to death from dehydration and shock. Ryan’s team theorized that antibodies in those who had been exposed somehow blocked the microorganism from swimming in the intestines, thus protecting the person from the disease.

To test the theory, Ryan and his colleagues spent five years analyzing antibodies recovered from people who survived cholera. "V. cholerae must be able to swim to reach the part of the intestine where it drops its toxin bomb,” explains Ryan. The researchers discovered that human antibodies blocked the bacterium from swimming by attacking the sugar coating that encapsulates the organism, including its long tail that propels it through the intestines.

It was the first time that scientists demonstrated that human antibodies could protect against a pathogen by stopping its movement through the body. Ryan and his team are now at work developing a vaccine that will elicit a long-term immune response to the V. cholerae’s sugar coating, including in children.

The investigators had little time to celebrate their breakthrough cholera discovery when COVID-19 became a global priority. Ryan’s entire lab, which is devoted to studying deadly and infectious pathogens, immediately shifted its focus. “Unlike many other research labs at MGH, ours was approved to stay open because our work could directly pivot to COVID,” says Ryan. Most of the cholera bench research was finished by the time COVID-19 hit, so the investigators spent their nights analyzing the cholera results and writing the manuscript before jumping back to COVID-19 each morning. “We ping-ponged between COVID and cholera,” says Ryan. “There were many long days.”

Ryan hopes that their discovery—that antibodies can stop the cholera bacterium from moving and causing disease—may also be important for stopping other moving pathogens.

Dispatches

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