Beta-defensin 2 enhances immunogenicity and protection of an adenovirus-based H5N1 influenza vaccine at an early time.

Beta-defensin 2 enhances immunogenicity and protection of an adenovirus-based H5N1 influenza vaccine at an early time.
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DOI:
10.1016/j.virusres.2013.09.013
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发表时间:
2013-12-26
期刊:
影响因子:
5
通讯作者:
Mittal SK
Mittal SK
中科院分区:
医学3区
文献类型:
--
作者:
Vemula SV;Amen O;Katz JM;Donis R;Sambhara S;Mittal SK

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亚洲和非洲许多国家人类感染高致病性 H5N1 禽流感病毒的报告显示,这些病毒具有不同程度的病死率,凸显了这些病毒的大流行潜力。为了在大流行情况下遏制流感病毒的快速传播,需要一种能够诱导快速、强烈免疫反应的疫苗,最好是单剂疫苗。鼠β-防御素 2 (Mbd2) 是一种由上皮细胞表达的小分子量蛋白质,已被证明可以通过招募和激活专业抗原呈递细胞到疫苗接种部位来增强抗原特异性免疫反应。本研究评估了 Mbd2 增强表达 H5N1 流感病毒血凝素 (HA) 和核蛋白 (NP) [HAd-HA-NP] 的人腺病毒 (HAd) 疫苗的免疫原性和保护功效的潜力。与仅接种 HAd-HA-NP 的组相比,对小鼠进行单次接种 HAd-HA-NP 和表达鼠 β-防御素 2 (HAd-Mbd2) 的 HAd 载体可导致体液和细胞介导的免疫反应水平显着升高。即使在免疫后第 7 天,这些反应也很明显。此外,接受最低载体剂量(2×107+1×107)的HAd-HA-NP+HAd-Mbd2免疫组在疫苗接种后第7天完全免受rgH5N1病毒攻击。这些结果凸显了 Mbd2 作为遗传佐剂在诱导针对基于 HAd 的疫苗的快速而强大的免疫反应方面的潜力。
Reports of human infections with highly pathogenic H5N1 avian influenza viruses in many countries in Asia and Africa with varying case fatality rates highlight the pandemic potential of these viruses. In order to contain a rapidly spreading influenza virus in a pandemic scenario, a vaccine which can induce rapid and robust immune responses, preferably in a single dose, is necessary. Murine beta-defensin 2 (Mbd2), a small molecular weight protein expressed by epithelial cells, has been shown to enhance antigen-specific immune responses by recruiting and activating professional antigen presenting cells to the site of vaccination. This study assessed the potential of Mbd2 to enhance the immunogenicity and protective efficacy of a human adenovirus (HAd)-based vaccine expressing the hemagglutinin (HA) and nucleoprotein (NP) [HAd-HA-NP] of an H5N1 influenza virus. A single inoculation of mice with both HAd-HA-NP and a HAd vector expressing Murine β-defensin 2 (HAd-Mbd2) resulted in significantly higher levels of both humoral and cell-mediated immune responses compared to the groups vaccinated only with HAd-HA-NP. These responses were evident even at Day 7 post-immunization. Furthermore, the HAd-HA-NP+HAd-Mbd2-immunized group receiving the lowest vector dose (2 × 107 + 1 × 107) was completely protected against an rgH5N1 virus challenge on Day 7 post-vaccination. These results highlight the potential of Mbd2 as a genetic adjuvant in inducing rapid and robust immune responses to a HAd-based vaccine.
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