Edible Cholera Vaccine Promising in Early Trial
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. The current study demonstrated that oral MucoRice-CTB induced toxin-specific antibodies that can block binding of the toxin to mammalian cells in vitro.

Researchers 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).

Participants given MucoRice-CTB showed increased CTB-specific serum IgG and IgA antibody concentrations without inducing serious adverse events, indicating that MucoRice-CTB could be a safe and potent vaccine to prevent diarrhoeal disease. MucoRice-CTB induced neutralising antibodies against diarrhoeal toxins in a gut microbiota-dependent manner. A similar phase 1 trial will be done with participants of other ethnicities to substantiate our findings.