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

被引:41
作者
Lee, Tae-Young [1 ]
Kim, Chang-Ung [1 ,2 ]
Bae, Eun-Hye [1 ]
Seo, Sang-Hwan [1 ]
Jeong, Dae Gwin [1 ,3 ]
Yoon, Sun-Woo [1 ,3 ]
Chang, Kyu-Tae [1 ]
Kim, Young Sang [2 ]
Kim, Sang-Hyun [4 ]
Kim, Doo-Jin [1 ,2 ,3 ]
机构
[1] KRIBB, Infect Dis Res Ctr, Daejeon, South Korea
[2] Chungnam Natl Univ, Dept Biochem, Daejeon, South Korea
[3] UST, Daejeon, South Korea
[4] Gyeongsang Natl Univ, Inst Anim Med, Coll Vet Med, Jinju, South Korea
关键词
Outer membrane vesicles; Influenza; Intranasal; Vaccine; Adjuvant; CD103(+) dendritic cells; DENDRITIC CELLS; CHOLERA-TOXIN; INDOLEAMINE 2,3-DIOXYGENASE; LYMPHOID-TISSUE; TH2; CELLS; RESPONSES; VIRUS; ADJUVANT; MICE; HEMAGGLUTININ;
D O I
10.1016/j.vaccine.2016.12.025
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:586 / 595
页数:10
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