壳聚糖水凝胶疫苗可产生针对小鼠黑色素瘤的保护性CD8 T细胞记忆。
Chitosan hydrogel vaccine generates protective CD8 T cell memory against mouse melanoma.
作者信息
Highton Andrew J, Kojarunchitt Thunjiradasiree, Girardin Adam, Hook Sarah, Kemp Roslyn A
机构信息
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
School of Pharmacy, University of Otago, Dunedin, New Zealand.
出版信息
Immunol Cell Biol. 2015 Aug;93(7):634-40. doi: 10.1038/icb.2015.14. Epub 2015 Feb 24.
CD8(+) T cells are important in the control of viral infections and cancers because of their cytolytic activity. A vaccine able to generate these cells could be beneficial in the prevention or treatment of these diseases. Chitosan hydrogel is a promising vaccine formulation that has previously been shown to generate effector CD8(+) T cells in a mouse model. This vaccine promotes sustained release of antigen and adjuvant, which generates a robust effector response. For longer lasting immunity, a memory population of these CD8(+) T cells is required to control further disease. We found that vaccination with chitosan hydrogel or dendritic cells using ovalbumin protein as a model antigen and Quil-A adjuvant provided protection in a subcutaneous melanoma challenge 30 days later. Ovalbumin-specific memory CD8(+) T cells were detectable following vaccination with the chitosan hydrogel but not the dendritic cell vaccine and an in vivo cytotoxicity assay demonstrated specific lysis of target cells in chitosan hydrogel vaccinated mice but not those receiving dendritic cell vaccination. These results demonstrate that vaccination with chitosan hydrogel is equally effective as dendritic cell vaccination in tumour protection but has more readily detectable immune correlates of protection. This may be advantageous in predetermining protection in vaccinated individuals.
CD8(+) T细胞因其细胞溶解活性在控制病毒感染和癌症方面发挥着重要作用。一种能够产生这些细胞的疫苗可能对预防或治疗这些疾病有益。壳聚糖水凝胶是一种很有前景的疫苗制剂,此前已在小鼠模型中证明其能产生效应性CD8(+) T细胞。这种疫苗可促进抗原和佐剂的持续释放,从而产生强烈的效应反应。为了获得更持久的免疫力,需要这些CD8(+) T细胞的记忆群体来控制后续疾病。我们发现,以卵清蛋白作为模型抗原、Quil-A作为佐剂,用壳聚糖水凝胶或树突状细胞进行疫苗接种,30天后在皮下黑色素瘤攻击试验中提供了保护作用。接种壳聚糖水凝胶疫苗后可检测到卵清蛋白特异性记忆CD8(+) T细胞,而接种树突状细胞疫苗后则未检测到,并且一项体内细胞毒性试验表明,接种壳聚糖水凝胶疫苗的小鼠体内靶细胞发生特异性裂解,而接种树突状细胞疫苗的小鼠则未出现这种情况。这些结果表明,壳聚糖水凝胶疫苗接种在肿瘤保护方面与树突状细胞疫苗接种同样有效,但具有更易于检测的保护免疫相关性。这在预先确定接种个体的保护情况方面可能具有优势。