dc.contributor.author | Teh, Audrey Y-H | |
dc.contributor.author | Cavacini, Lisa | |
dc.contributor.author | Hu, Yue | |
dc.contributor.author | Kumru, Ozan S. | |
dc.contributor.author | Xiong, Jian | |
dc.contributor.author | Bolick, David T. | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Grünwald-Gruber, Clemens | |
dc.contributor.author | Altmann, Friedrich | |
dc.contributor.author | Klempner, Mark | |
dc.contributor.author | Guerrant, Richard L. | |
dc.contributor.author | Volkin, David B. | |
dc.contributor.author | Wang, Yang | |
dc.contributor.author | Ma, Julian K-C. | |
dc.date.accessioned | 2022-01-10T20:36:52Z | |
dc.date.available | 2022-01-10T20:36:52Z | |
dc.date.issued | 2021-01-13 | |
dc.identifier.citation | Audrey Y-H Teh, Lisa Cavacini, Yue Hu, Ozan S. Kumru, Jian Xiong, David T. Bolick, Sangeeta B. Joshi, Clemens Grünwald-Gruber, Friedrich Altmann, Mark Klempner, Richard L. Guerrant, David B. Volkin, Yang Wang & Julian K-C. Ma (2021) Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants, Gut Microbes, 13:1, 1859813, DOI: 10.1080/19490976.2020.1859813 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32382 | |
dc.description.abstract | Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. SIgA1 and SIgA2 forms of mAb 68–81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. Susceptibility to gastric digestion was assessed in an in vitro model. Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. SIgA1 assembly appeared superior to SIgA2 in plants. Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68–61 SIgA1. The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs. | en_US |
dc.publisher | Taylor & Francis Open Access | en_US |
dc.rights | © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Enterotoxigenic Escherichia coli | en_US |
dc.subject | Monoclonal antibody | en_US |
dc.subject | Secretory IgA | en_US |
dc.subject | Passive immunization | en_US |
dc.subject | Immunotherapy | en_US |
dc.subject | Nicotiana benthamiana | en_US |
dc.title | Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Hu, Yue | |
kusw.kuauthor | Kumru, Ozan S. | |
kusw.kuauthor | Xiong, Jian | |
kusw.kuauthor | Joshi, Sangeeta B. | |
kusw.kuauthor | Volkin, David B. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1080/19490976.2020.1859813 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0001-9281-085X | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC7833773 | en_US |
dc.rights.accessrights | openAccess | en_US |