Oral MucoRice-CTB vaccine is safe and immunogenic in healthy US adults

Yoshikazu Yuki; Masanori Nojima; Koji Kashima; Kotomi Sugiura; Shinichi Maruyama; Shiho Kurokawa; Tomoyuki Yamanoue; Rika Nakahashi-Ouchida; Hiroyuki Nakajima; Takashi Hiraizumi; Hitoshi Kohno; Eiji Goto; Kohtaro Fujihashi; Hiroshi Kiyono

doi:10.1016/j.vaccine.2022.04.051

Oral MucoRice-CTB vaccine is safe and immunogenic in healthy US adults

Vaccine. 2022 May 26;40(24):3372-3379. doi: 10.1016/j.vaccine.2022.04.051. Epub 2022 Apr 26.

Affiliations

¹ Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
² Center for Translational Research, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
³ Asahi Kogyosha Co., Ltd., Tokyo, 105-0013, Japan.
⁴ Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Division of Mucosal Vaccines, International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
⁵ Graduate School of Horticulture, Chiba University, Chiba, Japan.
⁶ Division of Clinical Vaccinology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
⁷ Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Division of Mucosal Vaccines, International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Mucosal Immunology and Allergy Therapeutics, Institute for Global Prominent Research, Future Medicine Education and Research Organization, Chiba University, Chiba, 263-8522, Japan; CU-UCSD Center for Mucosal Immunology, Allergy, and Vaccine (cMAV) Division of Gastroenterology, Department of Medicine, University of California, San Diego, CA, 92093-0956, USA. Electronic address: kiyono@ims.u-tokyo.ac.jp.

PMID: 35484039
DOI: 10.1016/j.vaccine.2022.04.051

Abstract

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.

Keywords: Human study; MucoRice-CTB; Oral cholera vaccine; Plant-made pharmaceuticals; Transgenic rice.

Publication types

Clinical Trial, Phase I
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Cholera Toxin
Cholera Vaccines*
Enterotoxigenic Escherichia coli*
Female
Humans
Immunoglobulin A
Male
Oryza* / metabolism

Substances

Cholera Vaccines
Immunoglobulin A
Cholera Toxin