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A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment
Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679046/ https://www.ncbi.nlm.nih.gov/pubmed/23776657 http://dx.doi.org/10.1371/journal.pone.0066316 |
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author | Choi, Hyo-Jick Ebersbacher, Charles F. Kim, Min-Chul Kang, Sang-Moo Montemagno, Carlo D. |
author_facet | Choi, Hyo-Jick Ebersbacher, Charles F. Kim, Min-Chul Kang, Sang-Moo Montemagno, Carlo D. |
author_sort | Choi, Hyo-Jick |
collection | PubMed |
description | Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate and combined effects of temperature, retention time, pH, and osmotic stress on the stability of influenza vaccine by monitoring the time-dependent morphological change using stopped-flow light scattering. When exposed to osmotic stress, clustering of vaccine particles was enhanced in an acidic medium (pH 2.0) at ≥25°C. Fluorescence spectroscopic studies showed that hyper-osmotic stress at pH 2.0 and 37°C caused a considerable increase in conformational change of antigenic proteins compared to that in acidic iso-osmotic medium. A structural integrity of membrane was destroyed upon exposure to hyper-osmotic stress, leading to irreversible morphological change, as observed by undulation in stopped-flow light scattering intensity and transmission electron microscopy. Consistent with these analyses, hemagglutination activity decreased more significantly with an increasing magnitude of hyper-osmotic stress than in the presence of the hypo- and iso-osmotic stresses. This study shows that the magnitude and direction of the osmotic gradient has a substantial impact on the stability of orally administrated influenza vaccine. |
format | Online Article Text |
id | pubmed-3679046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36790462013-06-17 A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment Choi, Hyo-Jick Ebersbacher, Charles F. Kim, Min-Chul Kang, Sang-Moo Montemagno, Carlo D. PLoS One Research Article Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate and combined effects of temperature, retention time, pH, and osmotic stress on the stability of influenza vaccine by monitoring the time-dependent morphological change using stopped-flow light scattering. When exposed to osmotic stress, clustering of vaccine particles was enhanced in an acidic medium (pH 2.0) at ≥25°C. Fluorescence spectroscopic studies showed that hyper-osmotic stress at pH 2.0 and 37°C caused a considerable increase in conformational change of antigenic proteins compared to that in acidic iso-osmotic medium. A structural integrity of membrane was destroyed upon exposure to hyper-osmotic stress, leading to irreversible morphological change, as observed by undulation in stopped-flow light scattering intensity and transmission electron microscopy. Consistent with these analyses, hemagglutination activity decreased more significantly with an increasing magnitude of hyper-osmotic stress than in the presence of the hypo- and iso-osmotic stresses. This study shows that the magnitude and direction of the osmotic gradient has a substantial impact on the stability of orally administrated influenza vaccine. Public Library of Science 2013-06-11 /pmc/articles/PMC3679046/ /pubmed/23776657 http://dx.doi.org/10.1371/journal.pone.0066316 Text en © 2013 Choi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Choi, Hyo-Jick Ebersbacher, Charles F. Kim, Min-Chul Kang, Sang-Moo Montemagno, Carlo D. A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment |
title | A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment |
title_full | A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment |
title_fullStr | A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment |
title_full_unstemmed | A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment |
title_short | A Mechanistic Study on the Destabilization of Whole Inactivated Influenza Virus Vaccine in Gastric Environment |
title_sort | mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679046/ https://www.ncbi.nlm.nih.gov/pubmed/23776657 http://dx.doi.org/10.1371/journal.pone.0066316 |
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