Development of Antibody-Fragment-Producing Rice for Neutralization of Human Norovirus.

MucoRice norovirus transgenic rice variable-domain llama heavy-chain antibody fragment virus-like particle

Journal

Frontiers in plant science
ISSN: 1664-462X
Titre abrégé: Front Plant Sci
Pays: Switzerland
ID NLM: 101568200

Informations de publication

Date de publication:
2021
Historique:
received: 10 12 2020
accepted: 01 02 2021
entrez: 19 4 2021
pubmed: 20 4 2021
medline: 20 4 2021
Statut: epublish

Résumé

Human norovirus is the leading cause of acute nonbacterial gastroenteritis in people of all ages worldwide. Currently, no licensed norovirus vaccine, pharmaceutical drug, or therapy is available for the control of norovirus infection. Here, we used a rice transgenic system, MucoRice, to produce a variable domain of a llama heavy-chain antibody fragment (VHH) specific for human norovirus (MucoRice-VHH). VHH is a small heat- and acid-stable protein that resembles a monoclonal antibody. Consequently, VHHs have become attractive and useful antibodies (Abs) for oral immunotherapy against intestinal infectious diseases. MucoRice-VHH constructs were generated at high yields in rice seeds by using an overexpression system with RNA interference to suppress the production of the major rice endogenous storage proteins. The average production levels of monomeric VHH (7C6) to GII.4 norovirus and heterodimeric VHH (7C6-1E4) to GII.4 and GII.17 noroviruses in rice seed were 0.54 and 0.28% (w/w), respectively, as phosphate buffered saline (PBS)-soluble VHHs. By using a human norovirus propagation system in human induced pluripotent stem-cell-derived intestinal epithelial cells (IECs), we demonstrated the high neutralizing activity of MucoRice expressing monomeric VHH (7C6) against GII.4 norovirus and of heterodimeric VHH (7C6-1E4) against both GII.4 and GII.17 noroviruses. In addition, MucoRice-VHH (7C6-1E4) retained neutralizing activity even after heat treatment at 90°C for 20 min. These results build a fundamental platform for the continued development of MucoRice-VHH heterodimer as a candidate for oral immunotherapy and for prophylaxis against GII.4 and GII.17 noroviruses in not only healthy adults and children but also immunocompromised patients and the elderly.

Identifiants

DOI: 10.3389/fpls.2021.639953 PMID: 33868338 PMC: PMC8047661
pubmed: 33868338
doi: 10.3389/fpls.2021.639953
pmc: PMC8047661
doi:

Types de publication

Journal Article

Langues

eng

Pagination

639953

Informations de copyright

Copyright © 2021 Sasou, Yuki, Kurokawa, Sato, Goda, Uchida, Matsumoto, Sagara, Watanabe, Kuroda, Sakon, Sugiura, Nakahashi-Ouchida, Ushijima, Fujihashi and Kiyono.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Ai Sasou (A)

Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Yoshikazu Yuki (Y)

Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Mucosal Vaccines, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Shiho Kurokawa (S)

Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Shintaro Sato (S)

Division of Mucosal Vaccines, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Mucosal Vaccine Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Department of Immunology and Genomics, Graduate School of Medicine, Osaka City University, Osaka, Japan.

Yuki Goda (Y)

Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Masao Uchida (M)

Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.

Naomi Matsumoto (N)

Mucosal Vaccine Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

Hiroshi Sagara (H)

Medical Proteomics Laboratory, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Yuji Watanabe (Y)

Medical Proteomics Laboratory, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Masaharu Kuroda (M)

The National Agriculture and Food Research Organization, Tsukuba, Japan.

Naomi Sakon (N)

Department of Microbiology, Osaka Institute of Public Health, Osaka, Japan.

Kotomi Sugiura (K)

Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Rika Nakahashi-Ouchida (R)

Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Mucosal Vaccines, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Hiroshi Ushijima (H)

Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.

Kohtaro Fujihashi (K)

Division of Clinical Vaccinology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL, United States.

Hiroshi Kiyono (H)

Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Mucosal Vaccines, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Division of Gastroenterology, Department of Medicine, Chiba University - University of California San Diego Center for Mucosal Immunology, Allergy, and Vaccine, University of California, San Diego, San Diego, CA, United States.

Classifications MeSH