NEW YORK (Reuters Health) – MucoRice-CTB, a cholera toxin B subunit (CTB) vaccine made by grinding up genetically modified grains of rice, showed promise in a proof-of-concept study, researchers say.
“Although we have been developing the MucoRice-based oral vaccine since early 2000, we believe this is still just the beginning of our study for human applicability,” Dr. Hiroshi Kiyono of the University of Tokyo told Reuters Health by email. “It will require expanded clinical studies with different ethnic backgrounds in both industrial and developing countries.”
“Further,” he said, “we need to examine whether MucoRice-CTB-induced antibodies can control the toxin-caused diarrhea in pandemic regions. To this end, we recently conducted a phase IB study in the U.S. and we are currently analyzing the data.”
“The current study demonstrated that oral MucoRice-CTB induced toxin-specific antibodies that can block binding of the toxin to mammalian cells in vitro,” he noted. “However, we need to examine whether (these) antibodies prevent the cholera toxin that causes diarrhea in humans.”
As reported in The Lancet Microbe, Dr. Kiyono and colleagues conducted a randomized, placebo-controlled phase 1 single-center study in Tokyo. Six groups of 10 male volunteers, ages 18-40, received either 3 mg, 6 mg or 18 mg of the vaccine or placebo every two weeks. Women were excluded due to safety concerns.
The primary outcomes were safety and tolerability, measured by 12-lead electrocardiogram; vital signs; hematology, biochemistry, and urinalysis; rice protein-specific serum IgE antibody concentration; and adverse event monitoring.
Participants were assessed at baseline and at weeks 1, 2, 4, 6, 8, and 16.
Two participants given MucoRice-CTB 3 g and one given MucoRice-CTB 6 g were lost to follow-up and excluded from the efficacy analysis.
In those who received MucoRice-CTB 6 mg, serum CTB-specific IgG and IgA antibodies increased significantly in both a time- and dose-dependent manner compared to placebo.
A genomic analysis of feces before vaccination revealed that compared to non-responders, responders had a gut microbiota with higher diversity, including Escherichia coli and Shigella spp.
Twenty-eight participants (93%) who received any dose of MucoRice-CTB had at least one adverse event during the study, compared with 30 (100%) of 30 participants given placebo.
Grade 3 or higher adverse events were reported in four participants in the MucoRice-CTB group (five events) and four in the placebo group (10 events).
Decreased hemoglobin was the most common serious adverse event (two events in two participants each in the placebo and the pooled vaccine groups).
Dr. Kiyono noted that oral cholera vaccines are already available in some countries. Therefore, he suggested, future studies might include head-to-head comparisons, and/or a prime and boost strategy using different oral vaccines.
Dr. Peter Hotez, Dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston and Founding Editor-in-Chief of PLoS Neglected Tropical Diseases, commented on the study by phone. “We need innovative approaches, and looking at food sources for vaccine delivery is extremely interesting,” he said.
Complications include making certain that the vaccine is stable and that people get the same consistent dose, Dr. Hotez said. “Another issue is around the variability of vaccine uptake,” he said. “For example, the rotavirus vaccine often is not as effective when ingested by kids in low-income versus high-countries. Why is that? Is there a difference in gut microflora? Many things that influence this we don’t understand, including the forces that drive strong responses to orally delivered vaccines versus weak responses.”
“Having said that,” he added, “the only way to know is to continue to push that agenda. If we can get this oral vaccine to work and work consistently, it could be a game-changer for other gastrointestinal pathogens, including other bacteria such as E. coli, and even intestinal parasites.”
“We’ll have to see how it holds up in larger trials, and if they can define better the correlative protection – that is, the factors associated with the host microbiome or nutritional status that will influence how well the vaccine works,” Dr. Hotez concluded.
SOURCE: https://bit.ly/3jXyFz7 Lancet Microbe, online June 25, 2021.
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