image: Researchers from the University of Tokyo have announced the results of a phase I clinical trial of a new vaccine to prevent cholera and traveler’s diarrhea. view over
Credits: Images by Dr. Hiroshi Kiyono, CC BY 4.0
New vaccine to prevent cholera caused by grinding genetically modified rice grains The first human trials have shown no clear side effects and a favorable immune response. Researchers from the University of Tokyo and the University of Chiba have published the results of a peer reviewed clinical trial of a vaccine called MucoRice-CTB in Microbe Lancet.
Vaccine manufacturing has made great progress in 2020, fueled by COVID-1
9. However, the complexity of the mRNA-based SARS-CoV-2 vaccine underscores the value of vaccines that can be produced, transported and stored. It is cheap and does not need to be refrigerated.MucoRice-CTB vaccine is stable at room temperature from start to finish.
“I am very optimistic about the future of our MucoRice-CTB vaccine, especially because of the effect of increasing the dose. Participants responded to the low, medium, and high-dose vaccines, with the highest immune response at the highest dose,” said Professor Hiroshi Kiyono, DDS, Ph.D., from the University of Tokyo Institute of Medical Sciences. Leading the MucoRice project, Dr. Kiyono is also a professor at Chiba University in Japan and the University of California. San Diego in the United States
30 volunteers were given a placebo. and 10 subjects received a total of four vaccinations at intervals every 2 weeks, given either 3 milligrams (mg), 6 mg, or 18 mg, testing two and four months after the last dose. It revealed that the subjects who responded to the vaccine had antibodies IgA and IgG, two types of proteins the immune system makes to fight infection – specifically for cholera B (CTB). more likely to have CTB-specific antibodies
An independent review panel found no evidence of significant side effects.
The new vaccine, Vibrio cholerae, is most commonly spread by drinking contaminated water. without medical care Cholera can kill in a matter of hours due to severe diarrhea and dehydration. Cholera infects 1.3 million to 4 million people and causes 21,000 to 143,000 deaths each year, according to the World Health Organization.
There are four modern non-syringe cholera vaccines, all of which are administered as sublingual drops. Instead, it requires cold storage and is made from dead or whole (weak) cholera cells. https://
The new cholera vaccine is grown in genetically modified Japanese short-grain rice plants that produce benign CTB that is perceived by the immune system. The CTB is structurally similar to the toxin produced by some disease-causing E. coli bacteria. Therefore, the cholera vaccine often provides cross-protection against traveler’s diarrhea.
Researchers grow rice on purpose-built indoor hydroponics farms. This meets WHO standards for good drug manufacturing practice, which ensures that vaccines are not contaminated and plants are isolated from their natural environment.
Plants produce CTB subunits in seeds, edible grains. And the antigens are stored in aerosols known as lipid membrane-bound body proteins.
“Rice proteins look like natural capsules to deliver antigens to the immune system of the gut,” says Dr. Kiyono.
Other drugs are grown in plants, most often in the leaves. including treating Ebola lymphoma and influenza But the drug must be extracted and purified before being used. The appearance of cereals according to the MucoRice system avoids those extra steps. the need for cold storage and protect the antigens as they travel through the strong acidity of the stomach.
when the plant matures The rice is harvested and ground into a fine powder. Then sealed in aluminum wrap for storage. When people are ready to be vaccinated The powder is mixed with approximately 90 milliliters (1/3 US cup) of liquid and drunk. The researchers tested the vaccine using only saline. (Saline solution is equivalent to bodily fluid), but they expect the vaccine to be just as effective. together with plain water
Intestinal immunity is strong but complicated by the microbiome.
“The beautiful part of our vaccine is that it uses the body’s mucosal immune system through the gut to intelligently activate antigen-specific antibodies,” said Dr Kiyono.
MucoRice-CTB enters the body through the intestinal mucosa. by mimicking the natural way of encountering and responding to pathogens Stimulating the mucosal immune system produces two types of antibodies, which identify the pathogen and target for elimination: IgG and IgA. Vaccines administered subcutaneously or intramuscularly generally only add IgG, not IgA, which is an antibody.
Volunteers responding to MucoRice-CTB had the highest serum antigen-specific IgG and IgA levels after eight to 16 weeks.
However, 11 of the 30 vaccinated subjects had a low or no immune response. All study volunteers reported never leaving Japan. Therefore, it is unlikely that they have been exposed to pathogenic V. cholerae or E. coli before.
“When we saw those data about 11 low and unresponsive characters. We think the gut microbiome may influence the outcome of the immune response,” said Dr. Kiyono.
A microbe, or microbiome, is a community of microorganisms that live in our bodies and either benefit us or harm us. It is well established that the microflora in the digestive system influences health and immunity. But scientists are just beginning to understand the precise mechanisms of the relationship.
A detailed genetic analysis of all volunteers’ fecal samples identified thousands of bacteria that lived in the volunteers’ guts.
Dr. Kiyono said “In an easy-to-understand sense Those with high responses had more diverse microbes. and in the low-response group The diversity is much narrower.”
Researchers caution that the small size of the Phase I study, which vaccinated only 30 healthy Japanese male volunteers, means that the relevance and prevalence of those who do not respond are unclear. And overall differences in microbial diversity are uncomplicated. However, the findings highlight a greater role of microbes in vaccine effectiveness.
“Right now it’s just speculation. But perhaps higher microbial diversity creates a better situation for stronger immune responses to oral vaccines,” said Dr Kiyono.
The link between the gut microbiome and vaccine effectiveness was previously revealed by the unfortunate fact that most vaccines have been developed in industrialized countries. And some are less efficient when delivered in developing countries. mucosal vaccine including polio and cholera vaccines There is a tendency for this particular inequality. Most of the scientific theories explaining this phenomenon focus on chronic intestinal inflammation linked to poor sanitation (https://
Dr. Kiyono said, “Probably for all vaccinations now even injected vaccines We should think of an individual’s immune status based on the condition of their microbiome.
It remains to be seen how microbial diversity will affect the global performance of the new edible MucoRice vaccine system. Compared to other oral vaccine records
For now, the researchers plan to work with pharmaceutical industry partners to bring MucoRice-CTB into its next phase of clinical trials in Japan and overseas.
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research results
Yoshikazu Yuki, Masanori Nojima, Osamu Hosono, Hirotoshi Tanaka, Yasumasa Kimura, Takeshi Satoh, Seiya Imoto, Satoshi Uematsu, Shiho Kurokawa, Koji Kashima, Mio Mejima, Rika Nakahashi-Ouchida, Yohei Uchida, Takanori Marui, Noritada Yoshi. Ro, Fumitaka, Hiroshi Kiyono 24 June 2021 Evaluation of the oral MucoRice-CTB vaccine for safety and microbial-dependent immunization in humans: a randomized trial. Microbe Lancet.
Related links
Mucosal Immunology Division: https://
Society for Mucosal Immunology Oral History Interview: https://
contact research
Professor Hiroshi Kiyono, DDS, Ph.D.
Special Professor Unit, IMSUT, Division of Mucosal Immunology International Research and Development Center for Mucosal Vaccines Institute
medical science University of Tokyo 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Tel: +81-03-5449-5271
Email: kiyono@ims.u-tokyo.ac.jp
Contact the public relations officer
Mr Caitlin Devor
Public Relations Strategy Division, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 133-8654, JAPAN
Tel: +81-080-9707-8178
Email: press-releases.adm@gs.mail.u-tokyo.ac.jp
About the University of Tokyo
The University of Tokyo is Japan’s leading university and one of the world’s leading research universities. The enormous research results of approximately 6,000 researchers are published in the world’s leading journals in the arts and sciences. Our vibrant student body comprises approximately 15,000 undergraduate and 15,000 graduate students, as well as more than 4,000 international students.
funder
Japan Medical Research and Development Agency (AMED), Ministry of Education, Culture, Sports, Science and Technology (MEXT), Science and Technology Research Cooperation for Sustainable Development (SATREPS)
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