New edible cholera vaccine that can be transported and stored at room temperature has passed Phase 1 of clinical trials and demonstrated good immune response without obvious side effects.
Cholera infects 1.3 to 4 million people and is responsible for 21,000 to 143,000 deaths annually. Despite being an easily treatable disease, a lack of medical attention can lead to death in mere hours after infection due to diarrhoea with severe dehydration.
At present, there are four modern needle-free cholera vaccines available, all of which are administered via drops. However, these four vaccines require cold storage and are made from completely killed or weakened versions of the Vibrio cholerae bacteria. Fortunately, a new type of edible cholera vaccine named MucoRice-CTB has been developed to overcome these limitations and just recently passed Phase 1 of human clinical trials at the University of Tokyo.
About the MucoRice-CTB Vaccine
The MucoRice-CTB vaccine is made from genetically modified Japanese short-grain rice plants grown in hydroponic farms that have been approved by the World Health Organization. Once the rice plants mature, they can be harvested and grounded to fine powder, after which they can be stored in aluminium packets before use during vaccinations. The powder vaccine can be mixed with 90 millilitres of liquid and immediately drunk. Although the latest trial mixed the powdered vaccine with saline or salt solution, experts believe that it can be consumed with water as well.
Scientists specially engineered these rice plants to produce non-toxic levels of Cholera Toxin B (CTB) subunits in their seeds and store the antigens in protein bodies with lipid membranes. This unique feature allows the vaccine to skip conventional steps of extraction and purification, and be stored and transported at room temperature.
Professor Hiroshi Kiyono, D.D.S., Ph.D., from the Institute of Medical Science at the University of Tokyo, who is also the leader of the MucoRice project, explained how the rice protein bodies behave like a natural capsule, providing a protective layer for the antigens as they travel through the acidic environment of the stomach to the gut immune system. MucoRice-CTB acts on the intestinal mucosal membranes, stimulating the mucosal immune system to produce IgA and IgG antibodies.
Besides boosting immunity against cholera, this edible vaccine is also capable of providing cross-protective immunity against travellers’ diarrhoea since CTB is similar in structure to a toxin produced by some disease-causing Escherichia coli bacteria.
Results from the MucoRice-CTB Phase 1 Trial
In the latest Phase 1 trial, the MucoRice-CTB vaccine was reported to initiate a good immune response without posing any significant side effects. Of the 40 volunteers involved in the clinical trials, 30 were given placebo treatments while 10 were administered a complete dosage of MucoRice-CTB, which was a total of four doses spaced every two weeks of either 3 milligrams (mg), 6 mg, or 18 mg per dose.
The researchers followed up with the volunteers two and four months after the last dose was administered to confirm the efficacy of the vaccine. Their findings revealed that volunteers who responded to the rice vaccine successfully developed CTB-specific IgA and IgG antibodies, and those who received a higher dose of the vaccine were more likely to exhibit a greater immune response. High responders demonstrated the highest levels of antigen-specific IgG and IgA eight to 16 weeks after the dose.
“I’m very optimistic for the future of our MucoRice-CTB vaccine, especially because of the dose-escalation results. Participants responded to the vaccine at the low, medium and high doses, with the largest immune response at the highest dose,” said Professor Kiyono.
However, not all of the volunteers demonstrated a good immune response, as 11 of the 30 volunteers who received the vaccine exhibited low or no measurable immune response. After conducting an extensive genetic analysis of the volunteers’ fecal samples, it was revealed that high responders had more diversified gut microflora, while the low-responder group exhibited a narrower diversity.
This observation has led the scientists to speculate that the gut microflora may be responsible for poor immune response and that higher microflora diversity may create a favourable environment for the stronger immune response against oral vaccines.
While it remains to be seen how microflora diversity will affect future vaccinations, the team plans to push ahead with the next phase of clinical trials for MucoRice-CTB in Japan and overseas in hopes of bringing this novel vaccine into clinical practice. [APBN]
Source: Yuki et al. (2021). Oral MucoRice-CTB vaccine for safety and microbiota-dependent immunogenicity in humans: a phase 1 randomised trial. The Lancet Microbe.