Drink rather than vaccine may be cholera answer

A fast-acting, drinkable antidote for cholera epidemics is getting closer to being developed, according to two new studies.

Research published in PLOS Pathogens and ACS Infectious Disease, led by Ulf Yrlid, associate professor of immunology at Sahlgrenska Academy, Sweden, suggests a drinkable protective agent that would be distributed during an ongoing cholera epidemic.

The drink would block the cholera toxin so that it cannot reach the intestinal mucous membrane, the researchers say. It would be more effective than a vaccine, according to the study.

Yrlid, with colleagues in Gothenburg and a research team at the University of Texas Southwestern Medical Center in Dallas, USA, looked at the role of GM1, which is a specific receptor in the intestine.

It is believed that cholera toxin is dependent on GM1 to bind in the intestinal wall, which causes massive fluid loss through diarrhoea.

This research in mice has shown that those lacking GM1 also get diarrhoea after drinking water containing cholera toxin. Fluid loss could be prevented in human intestinal tissue exposed to cholera toxin by adding molecules that block binding to completely different receptors than GM1.

“The big takeaway for us is that we have shown that it’s not quite as simple as people have maintained for decades,” said Ulf Yrlid.

“GM1 is indeed a very powerful receptor in this context, but unlike the other receptors, there is very little of it in the human intestine.”

The results mean that a drinkable antidote that can put both GM1 and other receptors out of play could be a better option than a vaccine.

“The problem with vaccines is that they work less well in developing countries due to malnutrition and poor health, especially when it comes to small children. This is not unique for cholera vaccine, but applies to the entire field of vaccination,” says Yrlid.

“If we could use molecules that bind effectively to the cholera toxin and thereby prevent the toxin from attaching to the intestine, we could then immediately reduce the spreading in an affected area, even if people are not vaccinated or don’t have sufficient protection.

“One advantage of the molecules we modify is they are sugar molecules that already are present in breast milk to a great extent and therefore are safe to drink.”

Cervin J, Wands A, Casselbrant A et al. GM1 ganglioside-independent intoxication by Cholera toxin. PLOS Pathogens. March 2018.

Link: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006862

Wands A, Cervin J, Huang H et al. Fucosylated molecules competitively interfere with Cholera toxin binding to host cells. ACS Infectious Diseases March 2018.

Link: https://pubs.acs.org/doi/10.1021/acsinfecdis.7b00085

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