According to the World Health Organization, in 2018 the total of cholera cases registered worldwide decreased by 60%. This has been possible thanks to disease surveillance and containment strategies, dedicated to detect and stop outbreaks early, but also to serve the population with better hygienic and sanitary measures among which, of course, are the cholera vaccines. However, this disease is still a problem in some places with few economic resources and little health infrastructure, where something like keeping vaccines can be a challenge. This is why a team of scientists from the Universities of Tokyo and Chiba decided to look for innovative ways to develop cholera vaccines with the help of a resource as accessible as rice.
Injectables are the most complicated to store and manage, so there are already four alternatives consisting of drops that are dropped on the tongue. But they also need cold. What these scientists propose, therefore, goes further, since it is a edible vaccine, based crushed rice powder.
At the moment they have only exceeded first phase of clinical trials. There is still a long way to go, but the results obtained so far are very promising.
Why are new cholera vaccines so necessary?
Cholera is a digestive disease, caused by bacteria Vibrio cholerae, which is transmitted through the Non-potable water and contaminated food. It is characterized by the presence of very severe diarrhea, which can quickly cause dehydration and death of patients.
In fact, although it is practically unknown in developed countries, it is estimated that it causes between 21,000 and 143,000 deaths per year.
Cholera vaccines are an essential tool to stop these deaths. And thanks to the genetic engineering, in a few years we could have a totally innovative one.
Genetically modified rice grains
In search of easy-to-store and administer coronavirus vaccines, these scientists, whose results were just published in the Lancet Microbe, opted for an edible option, which they have dubbed MucoRice-CBT.
Rice is genetically modified so that a harmless version of a cholera toxin is synthesized in its cells
And, for this, they began by cultivating genetically modified rice so that a harmless alternative to the cholera bacteria toxin B. Thus, when someone consumes that rice, the disease is not generated. But his immune system it does recognize the toxin and react as if an infection had occurred. This reaction kills the synthesis of specific antibodies and memory cells that are prepared to launch the entire defensive battalion much faster in the event of another infection.
Once these rice plants are grown, the grains are ground to a very fine powder, which is stored in aluminum containers. This step does not require cold. Later, when it is going to be used, it is only necessary mix it with 90 milliliters of liquid. This mixture is what the patient drinks. So far in clinical trials that liquid has been a saline solution. However, they believe that the result would be the same with running water.
The method of administration is very important, since the rice grains store the toxin in droplets, called protein bodies, that pass directly to the digestive tract. Thus, they arrive as soon as possible at the place where the focus of the infection may occur in the future.
Finally, another interesting fact about this is that, unlike other cholera vaccines, it does not focus on the attenuated microorganism, but only on a toxin. On the one hand this avoids possible side effects. On the other hand, as this toxin has a structure similar to that of other bacteria, such as E.coli, it seems that it is generated cross protection against other diseases known as traveler’s diarrhea.
What has been done in the clinical trial?
As is customary in the first phase of clinical trials, this has been aimed at testing in a small group of patients the safety of the drug and the most appropriate dose.
There were no worrisome side effects and the best dose was the highest of those tested
Therefore, the 30 volunteers received four doses spaced two weeks apart, which could be of 3 mg, 6 mg or 18 mg. None of them caused worrisome side effects. In addition, all of them generated an immune response against the cholera bacteria, although the best one was that of the higher dose. This response was measured by analyzing the levels of two types of antibodies, IgA and IgG.
The only worrying fact was that there were 11 volunteers who had a low or no response. The reason is not yet known, but the study authors believe it may be related to the intestinal microbiota. That is, with the population of beneficial microorganisms that live in our digestive system. It is known to be closely linked to the effectiveness of the immune system, so it is somewhat plausible.
For this reason, in a press release they indicate that it will be very important to analyze this factor in the effectiveness of cholera vaccines, both in theirs and in the rest. For the time being, if applicable, they will need to conduct further trials with a larger group of patients. They explain that it is necessary because they understand that only 30 people are not enough to understand the influence of non-responders.
There is much to do; But, of course, this research shows how much we have to discover about vaccines. And it is that since Edward jenner vaccinated that first child with cowpox the history of vaccines has advanced by leaps and bounds. So far we have only eradicated one human disease. Precisely the smallpox that Jenner fought against. Others, like polio, are on the ropes, but one more step is missing. Science has advanced so much that in the face of the worst pandemic in the last century, we have had several vaccines in just one year. Now we also see that edible vaccines can be a useful alternative against certain diseases such as cholera. Without a doubt, we can be very proud of science.