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Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses

The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solv...

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Autores principales: Zhang, Yan, Yang, Jingyi, Bao, Rong, Chen, Yaoqing, Zhou, Dihan, He, Benxia, Zhong, Maohua, Li, Yaoming, Liu, Fang, Li, Qiaoli, Yang, Yi, Han, Chen, Sun, Ying, Cao, Yuan, Yan, Huimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174162/
https://www.ncbi.nlm.nih.gov/pubmed/21935396
http://dx.doi.org/10.1371/journal.pone.0024296
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author Zhang, Yan
Yang, Jingyi
Bao, Rong
Chen, Yaoqing
Zhou, Dihan
He, Benxia
Zhong, Maohua
Li, Yaoming
Liu, Fang
Li, Qiaoli
Yang, Yi
Han, Chen
Sun, Ying
Cao, Yuan
Yan, Huimin
author_facet Zhang, Yan
Yang, Jingyi
Bao, Rong
Chen, Yaoqing
Zhou, Dihan
He, Benxia
Zhong, Maohua
Li, Yaoming
Liu, Fang
Li, Qiaoli
Yang, Yi
Han, Chen
Sun, Ying
Cao, Yuan
Yan, Huimin
author_sort Zhang, Yan
collection PubMed
description The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.
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spelling pubmed-31741622011-09-20 Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses Zhang, Yan Yang, Jingyi Bao, Rong Chen, Yaoqing Zhou, Dihan He, Benxia Zhong, Maohua Li, Yaoming Liu, Fang Li, Qiaoli Yang, Yi Han, Chen Sun, Ying Cao, Yuan Yan, Huimin PLoS One Research Article The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies. Public Library of Science 2011-09-15 /pmc/articles/PMC3174162/ /pubmed/21935396 http://dx.doi.org/10.1371/journal.pone.0024296 Text en Zhang 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
Zhang, Yan
Yang, Jingyi
Bao, Rong
Chen, Yaoqing
Zhou, Dihan
He, Benxia
Zhong, Maohua
Li, Yaoming
Liu, Fang
Li, Qiaoli
Yang, Yi
Han, Chen
Sun, Ying
Cao, Yuan
Yan, Huimin
Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses
title Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses
title_full Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses
title_fullStr Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses
title_full_unstemmed Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses
title_short Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses
title_sort unpolarized release of vaccinia virus and hiv antigen by colchicine treatment enhances intranasal hiv antigen expression and mucosal humoral responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174162/
https://www.ncbi.nlm.nih.gov/pubmed/21935396
http://dx.doi.org/10.1371/journal.pone.0024296
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