Gierynska Malgorzata, Szulc-Dabrowska Lidia, Dzieciatkowski Tomasz, Golke Anna, Schollenberger Ada
Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786 Warsaw, Poland
Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786 Warsaw, Poland.
Pathog Dis. 2015 Dec;73(9):ftv088. doi: 10.1093/femspd/ftv088. Epub 2015 Oct 15.
Eradication of smallpox has led to cessation of vaccination programs. This has rendered the human population increasingly susceptible not only to variola virus infection but also to infections with other representatives of Poxviridae family that cause zoonotic variola-like diseases. Thus, new approaches for designing improved vaccine against smallpox are required. Discovering that orthopoxviruses, e.g. variola virus, vaccinia virus, ectromelia virus, share common immunodominant antigen, may result in the development of such a vaccine. In our study, the generation of antigen-specific CD8(+) T cells in mice during the acute and memory phase of the immune response was induced using the vaccinia virus immunodominant TSYKFESV epitope and CpG oligodeoxynucleotides as adjuvants. The role of the generated TSYKFESV-specific CD8(+) T cells was evaluated in mice during ectromelia virus infection using systemic and mucosal model. Moreover, the involvement of dendritic cells subsets in the adaptive immune response stimulation was assessed. Our results indicate that the TSYKFESV epitope/TLR9 agonist approach, delivered systemically or mucosally, generated strong CD8(+) T-cell response when measured 10 days after immunization. Furthermore, the TSYKFESV-specific cell population remained functionally active 2 months post-immunization, and gave cross-protection in virally challenged mice, even though the numbers of detectable antigen-specific T cells decreased.
天花的根除导致了疫苗接种计划的停止。这使得人类不仅越来越容易感染天花病毒,而且更容易感染痘病毒科其他可引起人畜共患天花样疾病的病毒。因此,需要设计改进型天花疫苗的新方法。发现正痘病毒,如天花病毒、痘苗病毒、鼠痘病毒,具有共同的免疫显性抗原,可能会促成此类疫苗的研发。在我们的研究中,使用痘苗病毒免疫显性TSYKFESV表位和CpG寡脱氧核苷酸作为佐剂,在小鼠免疫反应的急性期和记忆期诱导产生抗原特异性CD8(+) T细胞。利用全身和黏膜模型,在小鼠感染鼠痘病毒期间评估所产生的TSYKFESV特异性CD8(+) T细胞的作用。此外,还评估了树突状细胞亚群在适应性免疫反应刺激中的作用。我们的结果表明,在免疫后10天进行检测时,通过全身或黏膜途径递送的TSYKFESV表位/TLR9激动剂方法可产生强烈的CD8(+) T细胞反应。此外,TSYKFESV特异性细胞群体在免疫后2个月仍保持功能活性,并在病毒攻击的小鼠中提供交叉保护,尽管可检测到的抗原特异性T细胞数量有所减少。