Cholera is a devastating gastrointestinal infection that continues to afflict millions of people worldwide every year. An estimated 21,000 to 143,000 of these cases are fatal. Transmitted through contaminated fluids, the causative bacteria, Vibrio cholerae, colonizes the human gut with such terrifying speed that the symptoms of severe diarrhea and vomiting may arise mere hours after initial exposure. The resulting severe dehydration – an attempt by the overwhelmed body to flush out the bacteria’s potent toxin – will usually lead to death if rehydration therapy is not initiated quickly.
Both epidemic and low-level outbreaks of cholera occur whenever the bacterium finds its way into a water or food source that is not cleaned before consumption; an event that is worryingly common in underdeveloped nations and areas that have been hit by natural disasters. The current public health arsenal for cholera outbreak prevention is limited to promoting sanitary infrastructure and distribution of several vaccines, all of which must be administered twice, several days apart, and only confer full protection for a few months to two years.
But now, two separate research groups focused on developing better, next-generation vaccines have reported promising results from safety and efficacy tests conducted in animals. Their innovative approaches are described in studies published this week in Science Translational Medicine.
The team headed by Troy Hubbard of Harvard Medical School created an orally administered vaccine composed of live bacteria from a genetically modified version of a highly virulent Haitian strain, called HaitiV. Designed to colonize the intestines without inducing harmful effects, experiments in rabbits revealed that the vaccine protects against infection from dangerous, wild-type V. cholerae strains just 24 hours after dosing.
"What we've done is something very different than what others have done before. We don't yet fully understand how, but in our preclinical model this novel therapeutic protects against cholera-like illness less than a day after it is administered,” stated co-author Dr Matthew Waldor. He and his colleagues speculate that the presence of the HaitiV in the gut prevents strains introduced afterward from taking hold in the same environment, making it a type of competitive probiotic.
"The speed with which you respond to an outbreak significantly helps your ability to control that outbreak and prevent people from getting cholera," added Hubbard. "We are very focused on feasibility – the idea of being able to come in with a single-dose intervention that works rapidly but confers immunity over a long period of time is our target for the best possible vaccine."
Though future studies will need to examine the duration of HaitiV’s protection, the team is already looking into initiating a trial in human volunteers.
Also based upon the concept of a duking microbiome, the investigation led by Ning Mao of the Massachusetts Institute of Technology discovered that the common Lactococcus lactis bacteria – a lactic acid-producing species humans have been using to preserve foods for millennia – can inhibit proliferation of virulent cholera strains by lowering the pH of the gut. Their experiments in baby mice showed that regular intake of L. lactis supplements prevented the onset of cholera and treated existing infections.
“We found that V. cholerae-infected mice were substantially more likely to survive when they were co-inoculated with L. lactis (84.6%) compared to [control supplements] when they were mock-fed (45.7%),” they wrote.
The researchers anticipate that a line of probiotic L. lactis beverages or pills may soon provide an inexpensive and easy-to-implement defense against cholera.
If all goes according to plan, both these new vaccine candidates could help meet the World Health Organization’s goal of reducing cholera deaths by 90 percent by 2030.
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