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Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model

Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no e...

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Autores principales: Lee, Tae-Young, Kim, Chang-Ung, Bae, Eun-Hye, Seo, Sang-Hwan, Jeong, Dae Gwin, Yoon, Sun-Woo, Chang, Kyu-Tae, Kim, Young Sang, Kim, Sang-Hyun, Kim, Doo-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115551/
https://www.ncbi.nlm.nih.gov/pubmed/28024958
http://dx.doi.org/10.1016/j.vaccine.2016.12.025
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author Lee, Tae-Young
Kim, Chang-Ung
Bae, Eun-Hye
Seo, Sang-Hwan
Jeong, Dae Gwin
Yoon, Sun-Woo
Chang, Kyu-Tae
Kim, Young Sang
Kim, Sang-Hyun
Kim, Doo-Jin
author_facet Lee, Tae-Young
Kim, Chang-Ung
Bae, Eun-Hye
Seo, Sang-Hwan
Jeong, Dae Gwin
Yoon, Sun-Woo
Chang, Kyu-Tae
Kim, Young Sang
Kim, Sang-Hyun
Kim, Doo-Jin
author_sort Lee, Tae-Young
collection PubMed
description Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no effective killed or recombinant mucosal influenza vaccines to date. Outer membrane vesicles (OMVs) are nano-sized vesicles produced by gram-negative bacteria, and contain various bacterial components capable of stimulating the immune system of the host. We generated an OMV with low endotoxicity (fmOMV) by modifying the structure of the lipid A moiety of lipopolysaccharide and investigated its effect as an intranasal vaccine adjuvant in an influenza vaccine model. In this model, fmOMV exhibited reduced toll-like receptor 4-stimulating activity and attenuated endotoxicity compared to that of native OMV. Intranasal injection of the vaccine antigen with fmOMV significantly increased systemic antibody and T cell responses, mucosal IgA levels, and the frequency of lung-resident influenza-specific T cells. In addition, the number of antigen-bearing CD103(+) dendritic cells in the mediastinal lymph nodes was significantly increased after fmOMV co-administration. Notably, the mice co-immunized with fmOMV showed a significantly higher protection rate against challenge with a lethal dose of homologous or heterologous influenza viruses without adverse effects. These results show the potential of fmOMV as an effective mucosal adjuvant for intranasal vaccines.
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spelling pubmed-71155512020-04-02 Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model Lee, Tae-Young Kim, Chang-Ung Bae, Eun-Hye Seo, Sang-Hwan Jeong, Dae Gwin Yoon, Sun-Woo Chang, Kyu-Tae Kim, Young Sang Kim, Sang-Hyun Kim, Doo-Jin Vaccine Article Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no effective killed or recombinant mucosal influenza vaccines to date. Outer membrane vesicles (OMVs) are nano-sized vesicles produced by gram-negative bacteria, and contain various bacterial components capable of stimulating the immune system of the host. We generated an OMV with low endotoxicity (fmOMV) by modifying the structure of the lipid A moiety of lipopolysaccharide and investigated its effect as an intranasal vaccine adjuvant in an influenza vaccine model. In this model, fmOMV exhibited reduced toll-like receptor 4-stimulating activity and attenuated endotoxicity compared to that of native OMV. Intranasal injection of the vaccine antigen with fmOMV significantly increased systemic antibody and T cell responses, mucosal IgA levels, and the frequency of lung-resident influenza-specific T cells. In addition, the number of antigen-bearing CD103(+) dendritic cells in the mediastinal lymph nodes was significantly increased after fmOMV co-administration. Notably, the mice co-immunized with fmOMV showed a significantly higher protection rate against challenge with a lethal dose of homologous or heterologous influenza viruses without adverse effects. These results show the potential of fmOMV as an effective mucosal adjuvant for intranasal vaccines. Elsevier Ltd. 2017-01-23 2016-12-23 /pmc/articles/PMC7115551/ /pubmed/28024958 http://dx.doi.org/10.1016/j.vaccine.2016.12.025 Text en © 2016 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Lee, Tae-Young
Kim, Chang-Ung
Bae, Eun-Hye
Seo, Sang-Hwan
Jeong, Dae Gwin
Yoon, Sun-Woo
Chang, Kyu-Tae
Kim, Young Sang
Kim, Sang-Hyun
Kim, Doo-Jin
Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model
title Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model
title_full Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model
title_fullStr Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model
title_full_unstemmed Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model
title_short Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model
title_sort outer membrane vesicles harboring modified lipid a moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115551/
https://www.ncbi.nlm.nih.gov/pubmed/28024958
http://dx.doi.org/10.1016/j.vaccine.2016.12.025
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