疫苗诱导的粘膜和全身记忆NK/ILC引起SIV/SHIV感染风险降低
Mohammad Arif Rahman1, Isabela Silva de Castro1, Luca Schifanella1
1Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States.
删除V1的HIV疫苗增强粘膜内存的NK细胞和抗原反应ILCs,这对于降低SIV/SHIV感染风险至关重要. 这些免疫反应与保护和病毒载荷控制有关.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 病毒学 病毒学
背景情况:
- 针对人类免疫缺陷病毒 (SIV) 或人类免疫缺陷病毒 (HIV) 包膜蛋白的DNA/ALVAC/gp120平台疫苗的系统输送.
- 与V1-复制疫苗相比,V1-删除 (ΔV1) 疫苗在减少粘膜SIV或SHIV获得方面表现出更强的疗效.
研究的目的:
- 通过基于DNA/ALVAC/gp120的疫苗接种来研究粘膜和系统记忆类自然杀手 (NK) 细胞和抗原反应性先天性淋巴细胞 (ILCs) 的诱导.
- 确定这些免疫细胞在预防SIV/SHIV感染中的作用.
主要方法:
- 在接种疫苗后的粘膜和全身区内对类似记忆的NK细胞 (TNF-α+,CD107+) 和抗原反应性ILCs (IL-17+,NKp44+,IL-3+,IL-13+,IFN-γ+) 的分析.
- 免疫细胞种群与SIV/SHIV感染风险和病毒载荷控制的相关性.
- 血蛋白质组分析以确定与免疫细胞抑制或促进相关的因素.
主要成果:
- 与V1复制疫苗相比,ΔV1艾滋病毒疫苗诱导的粘膜TNF-α+和CD107+记忆类NK细胞水平较高.
- 粘膜内存样NK细胞,全身大酶B+内存NK细胞和特定的疫苗诱导的粘膜抗原反应性ILC子集 (IL-17+ NKp44+ ILCs,IL-17+ ILC3s,IL-13+ ILC2s) 与获得风险降低有关.
- 粘膜内存样NK细胞和特定的粘膜env-reactive ILC子集 (IFN-γ+ ILC1s,IL-13+ ILC2s) 与病毒载荷控制相关.
- 在接种疫苗后观察到全身和粘膜内存样NK细胞之间的正相关性.
- 粘膜和系统性类似记忆的NK细胞与V2特异性抗体依赖细胞细胞毒性 (ADCC) 反应相关.
- 增加的风险与粘膜PMA/Ionomycin诱导的IFN-γ+和CD107+NKG2A-NKp44-ILCs相关.
- 蛋白质组分析确定了与抑制保护性免疫反应相关的特定细胞因子 (例如,CCL-19,LT-α,IL-15,OLR1,CCL-3,OSM,IL-6,CXCL-9),而FLT3连接物促进了保护性IL-17+反应.
结论:
- 粘膜内存类NK细胞和包膜反应性ILC反应对于防止粘膜SIV/SHIV感染至关重要.
- 疫苗诱导的免疫反应,特别是涉及类似记忆的NK细胞和ILCs,在控制病毒感染方面发挥着重要作用.
- 了解影响这些免疫反应的因素可以为开发更有效的艾滋病毒疫苗提供信息.
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