Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
Center for Translational Research, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
Vaccine. 2022 May 26;40(24):3372-3379. doi: 10.1016/j.vaccine.2022.04.051. Epub 2022 Apr 26.
MucoRice-CTB is a promising cold-chain-free oral cholera vaccine candidate. Here, we report a double-blind, randomized, placebo-controlled, phase I study conducted in the USA in which vaccination with the 6-g dose of MucoRice-CTB induced cross-reactive antigen-specific antibodies against the B subunit of cholera toxin (CTB) and enterotoxigenic Escherichia coli heat-labile enterotoxin without inducing serious adverse events. This dosage was acceptably safe and tolerable in healthy men and women. In addition, it induced a CTB-specific IgA response in the saliva of two of the nine treated subjects; in one subject, the immunological kinetics of the salivary IgA were similar to those of the serum CTB-specific IgA. Antibodies from three of the five responders to the vaccine prevented CTB from binding its GM1 ganglioside receptor. These results are consistent with those of the phase I study in Japan, suggesting that oral MucoRice-CTB induces neutralizing antibodies against diarrheal toxins regardless of ethnicity.
木薯霍乱毒素 B 亚单位结合疫苗(MucoRice-CTB)是一种有前景的非冷链口服霍乱疫苗候选物。在此,我们报告了一项在美国进行的双盲、随机、安慰剂对照、I 期研究,结果表明,接种 6 剂木薯霍乱毒素 B 亚单位结合疫苗可诱导针对霍乱毒素 B 亚单位(CTB)和肠产毒性大肠埃希菌不耐热肠毒素的交叉反应性抗原特异性抗体,而不会引起严重的不良事件。该剂量在健康男性和女性中是可接受的安全且耐受的。此外,它在 9 名接受治疗的受试者中的 2 名受试者的唾液中诱导了 CTB 特异性 IgA 反应;在 1 名受试者中,唾液 IgA 的免疫动力学与血清 CTB 特异性 IgA 的免疫动力学相似。疫苗 5 名应答者中的 3 名的抗体可阻止 CTB 与其 GM1 神经节苷脂受体结合。这些结果与日本的 I 期研究结果一致,表明无论种族如何,口服木薯霍乱毒素 B 亚单位结合疫苗均可诱导针对腹泻毒素的中和抗体。