First vaccine of its kind protects children from deadly intestinal infections

ETVAX is the first vaccine offering significant protection against pathogens. E.coli in children

By Sahas Mehra edited by Lewis asked.

Enterotoxigenic infections Escherichia coli (ETEC) are the most common cause of traveler’s diarrheaand they usually cause childhood diarrhea in low-income areas. In children under five, whose immune systems are still developing, infections can lead to malnutrition; they cause up to 42,000 deaths per year. There may soon be a vaccine to protect against these infections.

In the Lancet Infectious Diseases Last month, scientists shared results from the first study to evaluate the safety and effectiveness of a vaccine controlling ETEC in a large pediatric population in The Gambia. The vaccine, called ETVAX, is one of the several in development to reduce ETEC infections in adults and children. ETVAX provided immunity against pathogens and had no adverse side effects.

ETEC bacteria have “adhesin” proteins that allow them to attach to the intestinal mucosa. The bacteria then release toxins, which cause watery diarrhea and abdominal cramps. In low-income countries, lack of access to sanitation and safe drinking water increases the risk of E.coli infections, leading to more child deaths and higher health care costs.

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An approved oral cholera vaccine, called Dukoral, provides partial protection against some forms of ETEC diarrhea, but “at present, there is no approved vaccine against cholera.” E.coli vaccine available to protect against all types of E.coli infections in humans,” says immunologist Ann-Mari Svennerholm of the University of Gothenburg in Sweden, co-author of the study. She notes that ETVAX is the first to show significant protection against E.coli infections in people.

Oral cholera vaccines contain “just a few different types of bacteria” to boost protection against, Svennerholm says. ETEC bacteria, on the other hand, have 26 distinct adhesin proteins and two types of toxins. For ETVAX, his research team created a formula using the four most common adhesin proteins, found in 80 percent of all enterotoxigenic proteins. E.coli. They combined the proteins with an inert part of a toxin and a component that stimulates intestinal immune responses. ETVAX was created by Scandinavia Biopharma. Some study authors own commercial rights to the vaccine and could receive a small royalty if it ultimately becomes a commercial product.

Previous studies have shown ETVAX to be safe and effective in smaller pediatric populations in Bangladesh and Zambia. [TL1] In the recent trial, 4,936 Gambian children aged six to 18 months received three doses of either the oral vaccine or a placebo, with follow-up spanning two years. Researchers randomly assigned children to receive either the vaccine or the placebo, and investigators did not know who received which.

ETVAX increased antibodies against several ETEC adhesin proteins, particularly after the third dose. It reduced episodes of moderate to severe diarrhea in ETEC by a modest 26 percent compared to the placebo group when cases of ETEC with co-infections with common intestinal pathogens such as Shigella, Cryptosporidium, rotavirus or a type of norovirus were excluded.

When researchers included these co-infections, ETVAX reduced moderate to severe diarrhea due to ETEC by 48 percent in all children and by 68 percent in infants younger than nine months. This highlights the importance of vaccinating young infants who have not acquired natural immunity to intestinal pathogens. Additionally, co-author Thomas Wierzba, professor of infectious diseases at Wake Forest School of Medicine, says ETVAX reduced moderate to severe diarrhea due to viruses, bacteria or other parasites by 21%. This suggests that the vaccine provides partial protection against several intestinal pathogens.

Epidemiologist David Sack of the Johns Hopkins Bloomberg School of Public Health, who was not involved in the study, believes it is a “high-quality study” because it used different outcomes to evaluate the vaccine. He notes that the mechanisms behind cross-protection against other pathogens, however, require further investigation. Amira Roess, professor of global health and epidemiology at George Mason University’s College of Public Health, says the research supports future clinical trials, but more work is needed to better characterize the causes of diarrheal illness in participants.

ETVAX will soon be evaluated in a phase 3 trial approved by the European Medicines Agency, which will recruit 5,800 infants aged six to nine months from low- and middle-income countries.