PDF(Pubmed)
Abstract：
Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, especially in sensitive host species and focused on unravelling protective mechanisms, will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient increase in IL-8 and IL-10 in serum observed after immunization might be correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T-cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel with the cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T-cell responses, the increased levels of antigen experienced in cytotoxic CD4 T cells observed after the challenge in immunized pigs might also contribute to controlling virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections.
摘要：
基于天然减毒或转基因病毒的非洲猪瘟病毒（ASFV）候选疫苗有可能产生保护性免疫反应，尽管对于什么定义了针对ASFV的保护性免疫反应尚无共识。研究,特别是在敏感的宿主物种中，专注于解开保护机制，将有助于开发更安全、更有效的疫苗。本研究提供了对皮内免疫诱导的细胞反应的表型和功能数据的详细分析，并随后使用天然减毒的田间菌株Lv17/WB/Rie1增强家猪，以及针对肌内攻击的潜在保护机制。基因型II亚美尼亚/07菌株。免疫后观察到的血清中IL-8和IL-10的短暂增加可能与存活相关。保护还与稳健的ASFV特异性多功能记忆T细胞反应有关，其中CD4CD8和CD8T细胞被鉴定为病毒特异性IFNγ和TNFα的主要细胞来源。与细胞因子反应平行，这些T细胞亚群也显示出特定的细胞毒性活性,如CD107a脱颗粒标志物的表达增加所证明的。随着病毒特异性多功能CD4CD8和CD8T细胞反应，免疫猪攻击后观察到的细胞毒性CD4T细胞中抗原水平升高,这也可能有助于通过靶向感染的抗原呈递细胞的杀伤机制控制毒力感染.未来的研究应阐明本研究中证明的记忆T细胞反应是否持续存在，并为进一步的ASFV感染提供长期保护。
