中文摘要:研究采用DnaK蛋白单独免疫C57BL/6J小鼠。皮下或者鼻内免疫能够诱导脾脏产生IFN-γ分泌型CD4(+) T细胞,但只有鼻内免疫能够诱导肺部产生IL-17释放型CD4(+) T细胞;采用DnaK蛋白进行鼻内免疫能够在肺部产生组织固有CD4(+) T细胞。研究结果表明,采用DnaK蛋白进行鼻内免疫能够诱导免疫缺陷型小鼠或免疫活性小鼠产生粘膜免疫反应;DnaK 免疫能够诱导产生与BCG相似的抗Mtb免疫反应,说明DnaK能够作为Mtb的备选疫苗应在人类临床进行应用。
外文摘要:Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the limited efficacy of the Mtb vaccine in current use, Bacillus Calmette-Guerin (BCG). To date, there is no available vaccine for immunocompromised individuals. Thus, there is an urgent need to develop a new vaccine candidate which can induce mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been shown to induce protective immunity against Mtb infection when administered by DNA vaccine; however, the protection is inferior to that induced by the BCG vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone. Subcutaneous or intranasal vaccination with DnaK generated IFN gamma-secreting CD4(+) T cells in the spleen, but only intranasal vaccination generated IL-17-releasing CD4(+) T cells in the lungs, even when circulating CD4(+) T cells were diminished. Furthermore, intranasal vaccination with DnaK generated tissue resident CD4(+) T cells in the lungs. Vaccination with DnaK alone resulted in protective immunity comparable to BCG vaccination against tuberculosis in mice. Our results demonstrate that intranasal vaccination with DnaK can generate mucosal immunity in immunocompromised or immunocompetent mice and DnaK vaccination can generate protection against Mtb similar to BCG, underscoring its potential utility as an Mtb vaccine candidate in humans.
外文关键词: tuberculosis, intranasal, DnaK, vaccine, immunodeficiency
作者:Chuang, YM; Pinn, ML; Karakousis, PC; Hung, CF
作者单位:美国约翰霍浦金斯大学
期刊名称:FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
期刊影响因子:4.3
出版年份:2018
出版刊次:2
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