凋亡相关斑点蛋白酶募集结构域对疫苗的作用研究

Effect of apoptosis-associated speck-like protein containing a caspase recruitment domain on vaccine efficacy: Overcoming the effects of its deficiency with aluminum hydroxide adjuvant

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中文摘要:凋亡相关斑点蛋白包含一个酶募集结构域(ASC),该酶募集结构域是炎性体的一个重要成分。研究采用不含铝佐剂的灭活流感疫苗和含明矾佐剂的HPV疫苗分析了ASC对疫苗免疫作用的影响。结果表明,首次免疫2周后,流感疫苗免疫的ASC(-/-)缺陷小鼠没有产生抗体滴度;加强免疫后,ASC(-/-)缺陷小鼠的抗体滴度只有野生小鼠的一半;ASC(-/-)缺陷小鼠无法产生抗流感疫苗的细胞毒性T-淋巴细胞反应;免疫后的ASC(-/-)缺陷小鼠也不能产生有效的对抗病毒的保护作用。携带明矾佐剂的HPV疫苗免疫ASC(-/-)缺陷小鼠后,产生了与野生小鼠相似的抗体滴度和T细胞增殖;不含明矾佐剂的HPV疫苗免疫后,ASC(-/-)缺陷小鼠产生的HPV-特异性抗体滴度比野生小鼠低3倍。这些研究表明,疫苗使用明矾作佐剂能够克服ASC-免疫缺陷状态。
外文摘要:Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine-induced humoral and cell-mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is one of the main components of inflammasomes, but it is not clear whether ASC affects the vaccine-induced immune response. Herein, we used two types of vaccines: inactivated influenza vaccine not formulated with alum, and HPV vaccine formulated with alum. We gave the vaccines to ASC knockout (ASC(-/-)) mice to investigate the role of ASC in vaccine efficacy. Influenza vaccine-immunized ASC(-/-) mice did not show antibody titers in week 2 after the first vaccination. After boosting, the antibody titer in ASC(-/-) mice was about half that in wild type (WT) mice. Furthermore, a cytotoxic T-lymphocyte response against influenza vaccine was not induced in ASC(-/-) mice. Therefore, vaccinated ASC(-/-) mice did not show effective protection against viral challenge. ASC(-/-) mice immunized with alum-formulated HPV vaccine showed similar antibody titers and T-cell proliferation compared with immunized WT mice. However, the HPV vaccine without alum induced up to threefold lower titers of HPV-specific antibody titers in ASC(-/-) mice compared with those in WT mice. These findings suggest that alum in vaccine can overcome the ASC-deficient condition.
外文关键词:alum, ASC, HPV vaccine, influenza vaccine
作者:Lee, DK; Lee, EY; Kim, RH; Kwak, HW; Kim, JY; Kim, H; Kang, KW; Lee, SM; Park, JH; Chang, J; Nam, JH
作者单位:韩国天主教大学
期刊名称:MICROBIOLOGY AND IMMUNOLOGY
期刊影响因子:1.57
出版年份:2018
出版刊次:3
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  1. 编译服务:动物支原体学
  2. 编译者:程金花
  3. 编译时间:2018-05-07