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在小鼠中,先天性和T细胞免疫反应与仿真血凝素分裂流感病毒疫苗接种

Kirill Vasilev¹, Eduard Puente-Massaguer¹, Irene Hoxie¹

¹Department of Microbiology, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY 10029, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.

|August 28, 2025

概括

化学血凝素 (cHA) 疫苗显示出普遍流感保护的潜力. 辅助疫苗诱导了更强的T细胞反应,但单独的T细胞无法阻止小鼠的病毒复制.

科学领域:

免疫学
疫苗学
病毒学

背景情况:

基于化学血凝素 (cHA) 的疫苗正在探索普遍的流感病毒保护.
之前的研究表明cHA疫苗刺激交叉反应抗体和T细胞反应.
在cHA疫苗诱导的保护中T细胞免疫的确切作用需要进一步研究.

研究的目的:

用cHA候选疫苗免疫小鼠的先天和抗原特异性T细胞反应的特征.
评估CpG 1018辅助剂对免疫反应和对异种流感的保护的影响.
通过被动转移和耗尽研究阐明T细胞对保护的贡献.

主要方法:

用组2的cHA候选疫苗 (cH15/3_HK14N2_HK14和cH4/3_HK14N2_HK14) 接种或不接种CpG 1018辅助剂对小鼠进行序列免疫.
分析先天性和T细胞免疫反应,包括细胞因子 (IFN-γ,IL-2,TNF-α,IL-4,IL-5,IL-13,IL-10) 和T淋巴细胞群 (CD4⁺).
异种病毒挑战,被动血清和T细胞转移实验,以及CD4+T细胞耗尽研究.

主要成果:

没有辅助剂的疫苗诱导了混合的Th1/ Th2反应;辅助剂的疫苗 (分裂/ CpG) 诱导了多功能CD4效应记忆T淋巴细胞的Th1偏振反应.
没有辅助剂的疫苗导致肺部Th2细胞因子和乙素的增加.
免疫血清的被动转移减少了体重减轻和病毒载荷;被动的T细胞转移调节了先天反应,但没有病毒复制或体重减轻;CD4+T细胞枯竭影响了细胞因子的产生和先天细胞动态,但没有病毒复制.

结论:

在cHA接种的小鼠中,CpG 1018辅助剂增强了Th1偏离的CD4⁺ T细胞反应.
虽然抗体有助于保护,但CD4⁺ T细胞在流感挑战期间起到调节先天免疫反应的作用.
需要进一步的研究,以完全定义基于cHA的通用流感疫苗中T细胞免疫的保护机制.

关键词:

CpG 1018 其他的树干流感其他:T细胞全球疫苗

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