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Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation
Oral administration of engineered immunoglobulins has the potential to prevent enteric pathogen-induced diarrhea in infants. To prevent infection, these antibodies need to survive functionally intact in the proteolytic environment of the gastrointestinal tract. This research examined both ex vivo an...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456970/ https://www.ncbi.nlm.nih.gov/pubmed/32923453 http://dx.doi.org/10.3389/fnut.2020.00130 |
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author | Sah, Baidya Nath P. Lueangsakulthai, Jiraporn Kim, Bum Jin Hauser, Benjamin R. Woo, Yeonhee Olyaei, Amy Aloia, Molly O'Connor, Ann Scottoline, Brian Pastey, Manoj K. Dallas, David C. |
author_facet | Sah, Baidya Nath P. Lueangsakulthai, Jiraporn Kim, Bum Jin Hauser, Benjamin R. Woo, Yeonhee Olyaei, Amy Aloia, Molly O'Connor, Ann Scottoline, Brian Pastey, Manoj K. Dallas, David C. |
author_sort | Sah, Baidya Nath P. |
collection | PubMed |
description | Oral administration of engineered immunoglobulins has the potential to prevent enteric pathogen-induced diarrhea in infants. To prevent infection, these antibodies need to survive functionally intact in the proteolytic environment of the gastrointestinal tract. This research examined both ex vivo and in vivo the functional survival across infant digestion of palivizumab, a model FDA-approved recombinant antibody against respiratory syncytial virus (RSV) F protein. Palivizumab-fortified feed (formula or human milk), infant gastric, and intestinal samples were incubated to simulate in vivo digestion (ex vivo digestion). Palivizumab-fortified human milk was also fed to infants, followed by collection of gastric and intestinal samples (in vivo digestion). Palivizumab was purified from the samples of digestate using protein G spin columns followed by filtration through molecular weight cut-off membranes (30 kDa). Palivizumab functional survival across ex vivo and in vivo digestion was determined via an anti-idiotype ELISA and an RSV plaque reduction neutralization test. Palivizumab concentration and RSV neutralization capacity both decreased when incubated in intestinal samples (ex vivo study). The concentration and neutralization activity of orally-supplemented palivizumab also decreased across infant digestion (in vivo study). These results indicate that if recombinant IgGs were selected for oral supplementation to prevent enteric infections, appropriate dosing would need to account for degradation occurring in the digestive system. Other antibody formats, structural changes, or encapsulation could enhance survival in the infant gastrointestinal tract. |
format | Online Article Text |
id | pubmed-7456970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74569702020-09-11 Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation Sah, Baidya Nath P. Lueangsakulthai, Jiraporn Kim, Bum Jin Hauser, Benjamin R. Woo, Yeonhee Olyaei, Amy Aloia, Molly O'Connor, Ann Scottoline, Brian Pastey, Manoj K. Dallas, David C. Front Nutr Nutrition Oral administration of engineered immunoglobulins has the potential to prevent enteric pathogen-induced diarrhea in infants. To prevent infection, these antibodies need to survive functionally intact in the proteolytic environment of the gastrointestinal tract. This research examined both ex vivo and in vivo the functional survival across infant digestion of palivizumab, a model FDA-approved recombinant antibody against respiratory syncytial virus (RSV) F protein. Palivizumab-fortified feed (formula or human milk), infant gastric, and intestinal samples were incubated to simulate in vivo digestion (ex vivo digestion). Palivizumab-fortified human milk was also fed to infants, followed by collection of gastric and intestinal samples (in vivo digestion). Palivizumab was purified from the samples of digestate using protein G spin columns followed by filtration through molecular weight cut-off membranes (30 kDa). Palivizumab functional survival across ex vivo and in vivo digestion was determined via an anti-idiotype ELISA and an RSV plaque reduction neutralization test. Palivizumab concentration and RSV neutralization capacity both decreased when incubated in intestinal samples (ex vivo study). The concentration and neutralization activity of orally-supplemented palivizumab also decreased across infant digestion (in vivo study). These results indicate that if recombinant IgGs were selected for oral supplementation to prevent enteric infections, appropriate dosing would need to account for degradation occurring in the digestive system. Other antibody formats, structural changes, or encapsulation could enhance survival in the infant gastrointestinal tract. Frontiers Media S.A. 2020-08-14 /pmc/articles/PMC7456970/ /pubmed/32923453 http://dx.doi.org/10.3389/fnut.2020.00130 Text en Copyright © 2020 Sah, Lueangsakulthai, Kim, Hauser, Woo, Olyaei, Aloia, O'Connor, Scottoline, Pastey and Dallas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Nutrition Sah, Baidya Nath P. Lueangsakulthai, Jiraporn Kim, Bum Jin Hauser, Benjamin R. Woo, Yeonhee Olyaei, Amy Aloia, Molly O'Connor, Ann Scottoline, Brian Pastey, Manoj K. Dallas, David C. Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation |
title | Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation |
title_full | Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation |
title_fullStr | Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation |
title_full_unstemmed | Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation |
title_short | Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation |
title_sort | partial degradation of recombinant antibody functional activity during infant gastrointestinal digestion: implications for oral antibody supplementation |
topic | Nutrition |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456970/ https://www.ncbi.nlm.nih.gov/pubmed/32923453 http://dx.doi.org/10.3389/fnut.2020.00130 |
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