Scientists Are Growing an Edible Cholera Vaccine in Rice
The world's attention has been focused on the coronavirus crisis but Yemen, Bangladesh and many others countries in Asia and Africa are also in the grips of another pandemic: cholera. The current cholera pandemic first emerged in the 1970s and has devastated many communities in low-income countries. Each year, cholera is responsible for an estimated 1.3 million to 4 million cases and 21,000 to 143,000 deaths worldwide.
Immunologist Hiroshi Kiyono and his team at the University of Tokyo hope they can be part of the solution: They're making a cholera vaccine out of rice.
"It is much less expensive than a traditional vaccine, by a long shot."
Cholera is caused by eating food or drinking water that's contaminated by the feces of a person infected with the cholera bacteria, Vibrio cholerae. The bacteria produces the cholera toxin in the intestines, leading to vomiting, diarrhea and severe dehydration. Cholera can kill within hours of infection if it if's not treated quickly.
Current cholera vaccines are mainly oral. The most common oral are given in two doses and are made out of animal or insect cells that are infected with killed or weakened cholera bacteria. Dukoral also includes cells infected with CTB, a non-harmful part of the cholera toxin. Scientists grow cells containing the cholera bacteria and the CTB in bioreactors, large tanks in which conditions can be carefully controlled.
These cholera vaccines offer moderate protection but it wears off relatively quickly. Cold storage can also be an issue. The most common oral vaccines can be stored at room temperature but only for 14 days.
"Current vaccines confer around 60% efficacy over five years post-vaccination," says Lucy Breakwell, who leads the U.S. Centers for Disease Control and Prevention's cholera work within Global Immunization Division. Given the limited protection, refrigeration issue, and the fact that current oral vaccines require two disease, delivery of cholera vaccines in a campaign or emergency setting can be challenging. "There is a need to develop and test new vaccines to improve public health response to cholera outbreaks."
A New Kind of Vaccine
Kiyono and scientists at Tokyo University are creating a new, plant-based cholera vaccine dubbed MucoRice-CTB. The researchers genetically modify rice so that it contains CTB, a non-harmful part of the cholera toxin. The rice is crushed into a powder, mixed with saline solution and then drunk. The digestive tract is lined with mucosal membranes which contain the mucosal immune system. The mucosal immune system gets trained to recognize the cholera toxin as the rice passes through the intestines.
The cholera toxin has two main parts: the A subunit, which is harmful, and the B subunit, also known as CTB, which is nontoxic but allows the cholera bacteria to attach to gut cells. By inducing CTB-specific antibodies, "we might be able to block the binding of the vaccine toxin to gut cells, leading to the prevention of the toxin causing diarrhea," Kiyono says.
Kiyono studies the immune responses that occur at mucosal membranes across the body. He chose to focus on cholera because he wanted to replicate the way traditional vaccines work to get mucosal membranes in the digestive tract to produce an immune response. The difference is that his team is creating a food-based vaccine to induce this immune response. They are also solely focusing on getting the vaccine to induce antibodies for the cholera toxin. Since the cholera toxin is responsible for bacteria sticking to gut cells, the hope is that they can stop this process by producing antibodies for the cholera toxin. Current cholera vaccines target the cholera bacteria or both the bacteria and the toxin.
David Pascual, an expert in infectious diseases and immunology at the University of Florida, thinks that the MucoRice vaccine has huge promise. "I truly believe that the development of a food-based vaccine can be effective. CTB has a natural affinity for sampling cells in the gut to adhere, be processed, and then stimulate our immune system, he says. "In addition to vaccinating the gut, MucoRice has the potential to touch other mucosal surfaces in the mouth, which can help generate an immune response locally in the mouth and distally in the gut."
Cost Effectiveness
Kiyono says the MucoRice vaccine is much cheaper to produce than a traditional vaccine. Current vaccines need expensive bioreactors to grow cell cultures under very controlled, sterile conditions. This makes them expensive to manufacture, as different types of cell cultures need to be grown in separate buildings to avoid any chance of contamination. MucoRice doesn't require such an expensive manufacturing process because the rice plants themselves act as bioreactors.
The MucoRice vaccine also doesn't require the high cost of cold storage. It can be stored at room temperature for up to three years unlike traditional vaccines. "Plant-based vaccine development platforms present an exciting tool to reduce vaccine manufacturing costs, expand vaccine shelf life, and remove refrigeration requirements, all of which are factors that can limit vaccine supply and accessibility," Breakwell says.
Kathleen Hefferon, a microbiologist at Cornell University agrees. "It is much less expensive than a traditional vaccine, by a long shot," she says. "The fact that it is made in rice means the vaccine can be stored for long periods on the shelf, without losing its activity."
A plant-based vaccine may even be able to address vaccine hesitancy, which has become a growing problem in recent years. Hefferon suggests that "using well-known food plants may serve to reduce the anxiety of some vaccine hesitant people."
Challenges of Plant Vaccines
Despite their advantages, no plant-based vaccines have been commercialized for human use. There are a number of reasons for this, ranging from the potential for too much variation in plants to the lack of facilities large enough to grow crops that comply with good manufacturing practices. Several plant vaccines for diseases like HIV and COVID-19 are in development, but they're still in early stages.
In developing the MucoRice vaccine, scientists at the University of Tokyo have tried to overcome some of the problems with plant vaccines. They've created a closed facility where they can grow rice plants directly in nutrient-rich water rather than soil. This ensures they can grow crops all year round in a space that satisfies regulations. There's also less chance for variation since the environment is tightly controlled.
Clinical Trials and Beyond
After successfully growing rice plants containing the vaccine, the team carried out their first clinical trial. It was completed early this year. Thirty participants received a placebo and 30 received the vaccine. They were all Japanese men between the ages of 20 and 40 years old. 60 percent produced antibodies against the cholera toxin with no side effects. It was a promising result. However, there are still some issues Kiyono's team need to address.
The vaccine may not provide enough protection on its own. The antigen in any vaccine is the substance it contains to induce an immune response. For the MucoRice vaccine, the antigen is not the cholera bacteria itself but the cholera toxin the bacteria produces.
"The development of the antigen in rice is innovative," says David Sack, a professor at John Hopkins University and expert in cholera vaccine development. "But antibodies against only the toxin have not been very protective. The major protective antigen is thought to be the LPS." LPS, or lipopolysaccharide, is a component of the outer wall of the cholera bacteria that plays an important role in eliciting an immune response.
The Japanese team is considering getting the rice to also express the O antigen, a core part of the LPS. Further investigation and clinical trials will look into improving the vaccine's efficacy.
Beyond cholera, Kiyono hopes that the vaccine platform could one day be used to make cost-effective vaccines for other pathogens, such as norovirus or coronavirus.
"We believe the MucoRice system may become a new generation of vaccine production, storage, and delivery system."
New Device Can Detect Peanut Allergens on a Plate in 30 Seconds
People with life-threatening allergies live in constant fear of coming into contact with deadly allergens. Researchers estimate that about 32 million Americans have food allergies, with the most severe being milk, egg, peanut, tree nuts, wheat, soy, fish, and shellfish.
"It is important to understand that just several years ago, this would not have been possible."
Every three minutes, a food allergy reaction sends someone to the emergency room, and 200,000 people in the U.S. require emergency medical care each year for allergic reactions, according to Food Allergy Research and Education.
But what if there was a way you could easily detect if something you were about to eat contains any harmful allergens? Thanks to Israeli scientists, this will soon be the case — at least for peanuts. The team has been working to develop a handheld device called Allerguard, which analyzes the vapors in your meal and can detect allergens in 30 seconds.
Leapsmag spoke with the founder and CTO of Allerguard, Guy Ayal, about the groundbreaking technology, how it works, and when it will be available to purchase.
What prompted you to create this device? Do you have a personal connection with severe food allergies?
Guy Ayal: My eldest daughter's best friend suffers from a severe food allergy, and I experienced first-hand the effect it has on the person and their immediate surroundings. Most notable for me was the effect on the quality of life – the experience of living in constant fear. Everything we do at Allerguard is basically to alleviate some of that fear.
How exactly does the device work?
The device is built on two main pillars. The first is the nano-chemical stage, in which we developed specially attuned nanoparticles that selectively adhere only to the specific molecules that we are looking for. Those molecules, once bound to the nanoparticles, induce a change in their electrical behavior, which is measured and analyzed by the second main pillar -- highly advanced machine learning algorithms, which can surmise which molecules were collected, and thus whether or not peanuts (or in the future, other allergens) were detected.
It is important to understand that just several years ago, this would not have been possible, because both the nano-chemistry, and especially the entire world of machine learning, big data, and what is commonly known as AI only started to exist in the '90s, and reached applicability for handheld devices only in the past few years.
Where are you at in the development process and when will the device be available to consumers?
We have concluded the proof of concept and proof of capability phase, when we demonstrated successful detection of the minimal known clinical amount that may cause the slightest effect in the most severely allergic person – less than 1 mg of peanut (actually it is 0.7 mg). Over the next 18 months will be productization, qualification, and validation of our device, which should be ready to market in the latter half of 2021. The sensor will be available in the U.S., and after a year in Europe and Canada.
The Allerguard was made possible through recent advances in machine learning, big data, and AI.
(Courtesy)
How much will it cost?
Our target price is about $200 for the device, with a disposable SenseCard that will run for at least a full day and cost about $1. That card is for a specific allergen and will work for multiple scans in a day, not just one time.
[At a later stage, the company will have sensors for other allergens like tree nuts, eggs, and milk, and they'll develop a multi-SenseCard that works for a few allergens at once.]
Are there any other devices on the market that do something similar to Allerguard?
No other devices are even close to supplying the level of service that we promise. All known methods for allergen detection rely on sampling of the food, which is a viable solution for homogenous foodstuffs, such as a factory testing their raw ingredients, but not for something as heterogenous as an actual dish – especially not for solid allergens such as peanuts, treenuts, or sesame.
If there is a single peanut in your plate, and you sample from anywhere on that plate which is not where that peanut is located, you will find that your sample is perfectly clean – because it is. But the dish is not. That dish is a death trap for an allergic person. Allerguard is the only suggested solution that could indeed detect that peanut, no matter where in that plate it is hiding.
Anything else readers should know?
Our first-generation product will be for peanuts only. You have to understand, we are still a start-up company, and if we don't concentrate our limited resources to one specific goal, we will not be able to achieve anything at all. Once we are ready to market our first device, the peanut detector, we will be able to start the R&D for the 2nd product, which will be for another allergen – most likely tree nuts and/or sesame, but that will probably be in debate until we actually start it.
[Ed. Note: This is the fourth episode in our Moonshot series, which explores four cutting-edge scientific developments that stand to fundamentally transform our world.]
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.