Japanese researchers have developed a new type of cholera vaccine by genetically modifying rice to carry a non-toxic cholera antigen. The vaccine needs no refrigeration with the rice simply ground into a powder, mixed with water and consumed.
The new vaccine first involved genetically engineering short-grain rice plants to produce cholera toxin subunit B (CTB). This part of the cholera toxin is often used for cholera vaccines as it is non-toxic but can induce potent immunity against the symptoms of a cholera infection.
The vaccine, called MucoRice-CTB, involves simply grinding up the engineered rice and mixing the powder into liquid. As rice stores its proteins in tiny membranes called protein bodies, the cholera antigens are naturally protected from digestive enzymes that would normally destroy other orally delivered vaccines.
"The rice protein bodies behave like a natural capsule to deliver the antigen to the gut immune system," explains Hiroshi Kiyono, a researcher working on the project.
A new study published in the journal The Lancet Microbe is detailing the results of the first phase 1 human trial testing MucoRice-CTB. The dose-response safety trial recruited four groups of 10 volunteers. Each group, apart from the placebo control, received a different dose of the vaccine. Four doses over eight weeks were given to each volunteer.
The study reports no significant side effects were caused by the novel vaccine, and the cohort showed positive dose-dependent immune responses with the largest response at the highest dose.
Around one-third of the total cohort receiving the vaccine showed minimal immune responses. Kiyono says this led the research team to hypothesize whether the composition of each individual gut microbiome could be playing a role in the vaccine’s efficacy.
"When we saw those data about the 11 low and nonresponders, we thought maybe gut microflora have an influence on the outcome of the immune response," says Kiyono.
Studying the microbial flora of the volunteers did not reveal any specific bacterial species as common to the vaccine nonresponders. The only factor the researchers could use to differentiate vaccine efficacy was overall microbial diversity.
"In simplified terms, high responders had more diversified microflora, and in the low-responder group, diversity was much narrower," says Kiyono. "It's all speculation right now, but maybe higher microflora diversity creates a better situation for strong immune response against oral vaccine.”
Kiyono points out this small phase 1 trial only recruited young, healthy Japanese men. A similar phase 1 trial is currently planned looking at safety and efficacy in other ethnicities. If this vaccine is to be deployed in the real-world then it will be crucial to understand how gut flora influences its efficacy, particularly since microbiome differences could be significant in low-income regions where cholera is endemic.
Although there are other oral cholera vaccines available, MucoRice-CTB is the only vaccine that does not require refrigeration. Eliminating cold storage from a supply line would make distribution significantly easier in remote countries. Plus, MucoRice-CTB can be manufactured cheaply making it a promising new prospective tool to battle a disease that still kills over 100,000 people every year.
The new study was published in the journal The Lancet Microbe.
Source: University of Tokyo