GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.
GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.
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DOI：
10.1371/journal.pone.0011021
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发表时间：
2010-06-08
期刊：
影响因子：
3.7
通讯作者：
Fuller DH
中科院分区：
文献类型：
--
作者：
Loudon PT;Yager EJ;Lynch DT;Narendran A;Stagnar C;Franchini AM;Fuller JT;White PA;Nyuandi J;Wiley CA;Murphey-Corb M;Fuller DH
最近H5N1禽流感和H1N1猪源性流感病毒暴发再次表明，全球流感大流行的威胁是真实存在的，而且永远存在。疫苗接种仍然被认为是预防流感病毒感染的最佳策略，但一项重大挑战是确定新的疫苗方法，以提供加速生产，更广泛地保护免受漂移和转移的毒株，以及在病毒进入部位引起呼吸道抗病毒免疫反应的能力。作为一种安全的减毒活疫苗替代品，采用颗粒介导表皮递送（PMED或基因枪）给药的H1N1流感（a/新喀里多尼亚/20/99）HA DNA疫苗在恒河猴体内的粘膜和全身免疫原性进行了分析。猕猴在第0周、第8周和第16周使用一次性一次性颗粒介导的递送装置进行免疫，该装置设计用于临床使用，可将质粒DNA直接递送到表皮细胞中。在1-3剂PMED HA DNA疫苗后，在猕猴外周血中观察到显著水平的血凝抑制（HI）抗体和分泌HA特异性细胞因子的T细胞。此外，HA DNA疫苗接种在接种的猕猴肺和肠道相关淋巴组织中诱导可检测水平的HA特异性粘膜抗体和T细胞。重要的是，共递送编码恒河猴GM-CSF基因的DNA可显著增强HA DNA疫苗的全身和粘膜免疫原性。这些结果为颗粒介导的表皮DNA疫苗的开发提供了强有力的支持，以防止呼吸道病原体（如流感）的感染，并首次证明了皮肤递送的GM-CSF作为疫苗诱导肠道和呼吸道免疫反应的有效粘膜佐剂的能力。
The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99) HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun) was analyzed in rhesus macaques. Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI) antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1–3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine. These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.
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影响因子：
3.1
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