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Japanese researchers have developed a new type of cholera vaccine by genetically modifying rice to carry a nontoxic cholera antigen. The vaccine does not need to be refrigerated, as the rice is simply ground into a powder, mixed with water and consumed.
The new vaccine first involved genetically modifying short-grain rice plants to produce the cholera toxin (CTB) B subunit. This part of the cholera toxin is often used for cholera vaccines because it is not toxic but can induce strong immunity against the symptoms of cholera infection.
The vaccine, called MucoRice-CTB, simply involves grinding the modified rice and mixing the powder into a liquid. Because rice stores its protein in tiny membranes called protein bodies, cholera antigens are naturally protected from digestive enzymes that would normally destroy other vaccines given by mouth.
“The protein bodies in rice behave like a natural capsule to deliver the antigen to the intestinal immune system,” explains Hiroshi Kiyono, researcher working on the project.
A new study published in the journal The Lancet Microbe details the results of the first human phase 1 trial testing MucoRice-CTB. The dose-response safety trial recruited four groups of 10 volunteers. Each group, except the placebo control, received a different dose of the vaccine. Four doses over eight weeks were administered to each volunteer.
The study reports that no significant side effects were caused by the new vaccine, and the cohort showed positive dose-dependent immune responses with the greatest response at the highest dose.
About a third of the total cohort receiving the vaccine showed minimal immune responses. Kiyono says this led the research team to hypothesize that the makeup of each individual gut microbiome might play a role in the vaccine’s effectiveness.
“When we saw this data on the weak 11 and the non-responders, we thought that the gut microflora might have been influencing the outcome of the immune response,” says Kiyono.
Hiroshi Kiyono
The study of the microbial flora of the volunteers did not reveal any specific bacterial species common to the non-responders to the vaccine. The only factor researchers could use to differentiate vaccine effectiveness was overall microbial diversity.
“Put simply, the high respondents had a more diverse microflora, and in the group of low respondents the diversity was much narrower,” says Kiyono. “This is only speculation at the moment, but perhaps a greater diversity of the microflora creates a better situation for a strong immune response against the oral vaccine.”
Kiyono points out that this small Phase 1 trial only recruited healthy young Japanese men. A similar Phase 1 trial is currently planned to examine safety and efficacy in other ethnicities. If this vaccine is to be deployed in the real world, understanding how the gut flora influences its effectiveness will be crucial, especially since microbiome differences could be significant in low-income areas where cholera is endemic.
Although there are other oral cholera vaccines, MucoRice-CTB is the only vaccine that does not require refrigeration. Removing cold storage from a supply line would greatly facilitate distribution in remote countries. What’s more, MucoRice-CTB can be manufactured inexpensively, making it a promising potential new tool in the fight against a disease that still kills more than 100,000 people each year.
The new study was published in the journal The Lancet Microbe.
Source: University of Tokyo
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