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...

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Autores principales:	Hyo-Jick Choi, Charles F Ebersbacher, Min-Chul Kim, Sang-Moo Kang, Carlo D Montemagno
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/14e3416410984453b32735516071269e
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spelling	oai:doaj.org-article:14e3416410984453b32735516071269e2021-11-18T07:42:13ZA mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment.1932-620310.1371/journal.pone.0066316https://doaj.org/article/14e3416410984453b32735516071269e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23776657/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Oral 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.Hyo-Jick ChoiCharles F EbersbacherMin-Chul KimSang-Moo KangCarlo D MontemagnoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66316 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyo-Jick Choi Charles F Ebersbacher Min-Chul Kim Sang-Moo Kang Carlo D Montemagno A mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment.
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	article
author	Hyo-Jick Choi Charles F Ebersbacher Min-Chul Kim Sang-Moo Kang Carlo D Montemagno
author_facet	Hyo-Jick Choi Charles F Ebersbacher Min-Chul Kim Sang-Moo Kang Carlo D Montemagno
author_sort	Hyo-Jick Choi
title	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_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_sort	mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/14e3416410984453b32735516071269e
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A mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment.

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