Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants
dc.contributor.author | Teh, Audrey Y-H. | |
dc.contributor.author | Cavacini, Lisa A. | |
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 | Grunwald-Gruber, Clemens | |
dc.contributor.author | Altmann, Friedrich | |
dc.contributor.author | Klempner, Mark S. | |
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 | 2022-08-11T08:09:58.000 | |
dc.date.accessioned | 2022-08-23T16:50:53Z | |
dc.date.available | 2022-08-23T16:50:53Z | |
dc.date.issued | 2021-01-13 | |
dc.date.submitted | 2021-03-11 | |
dc.identifier.citation | <p>Teh AY, Cavacini L, Hu Y, Kumru OS, Xiong J, Bolick DT, Joshi SB, Grünwald-Gruber C, Altmann F, Klempner M, Guerrant RL, Volkin DB, Wang Y, Ma JK. Investigation of a monoclonal antibody against enterotoxigenic <em>Escherichia coli</em>, expressed as secretory IgA1 and IgA2 in plants. Gut Microbes. 2021 Jan-Dec;13(1):1-14. doi: 10.1080/19490976.2020.1859813. PMID: 33439092; PMCID: PMC7833773. <a href="https://doi.org/10.1080/19490976.2020.1859813">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 1949-0976 (Linking) | |
dc.identifier.doi | 10.1080/19490976.2020.1859813 | |
dc.identifier.pmid | 33439092 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/41746 | |
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. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=33439092&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.rights | © 2021 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Enterotoxigenic Escherichia coli | |
dc.subject | Nicotiana benthamiana | |
dc.subject | immunotherapy | |
dc.subject | monoclonal antibody | |
dc.subject | passive immunization | |
dc.subject | secretory IgA | |
dc.subject | Amino Acids, Peptides, and Proteins | |
dc.subject | Bacteria | |
dc.subject | Bacterial Infections and Mycoses | |
dc.subject | Biological Factors | |
dc.subject | Immunotherapy | |
dc.title | Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants | |
dc.type | Journal Article | |
dc.source.journaltitle | Gut microbes | |
dc.source.volume | 13 | |
dc.source.issue | 1 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5571&context=oapubs&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/oapubs/4540 | |
dc.identifier.contextkey | 22022754 | |
refterms.dateFOA | 2022-08-23T16:50:53Z | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | oapubs/4540 | |
dc.contributor.department | MassBiologics | |
dc.source.pages | 1-14 |