肺表面活性剂-仿生纳米颗粒增强异型流感免疫力
Ji Wang1,2, Peiyu Li1,3, Yang Yu1
1Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA.
Science (New York, N.Y.)
|February 22, 2020
概括
这项研究引入了一种新型辅助剂,即具有cGAMP (PS- GAMP) 的肺表面活性剂- 仿生脂质体,以提高流感疫苗的疗效. 这种新辅助剂提供广泛的,持久的对抗不同流感菌株的交叉保护.
科学领域:
- 免疫学
- 疫苗学
- 纳米技术
背景情况:
- 目前的流感疫苗仅对同类菌株提供有限的保护.
- 需要疫苗辅助剂,可对各种流感亚型产生广泛而持久的交叉保护.
- STING (干扰素基因刺激剂) 激动剂具有增强疫苗诱导免疫力的潜力.
研究的目的:
- 开发和评估一种新型的肺表面活性剂 (PS) - 生物模拟脂质体封装cGAMP (PS-GAMP) 作为流感疫苗的辅助剂.
- 评估PS-GAMP增强幽默和CD8+T细胞对流感的反应的能力.
- 确定PS-GAMP辅助疫苗对异型亚型流感菌株的交叉保护效果.
主要方法:
- 合成封装cGAMP的PS仿生脂质体 (PS-GAMP).
- 用PS-GAMP辅助的H1N1疫苗对小鼠进行鼻腔免疫.
- 对幽默和CD8+T细胞免疫反应的评估,包括对H1N1,H3N2,H5N1和H7N9病毒的交叉保护测定.
- 在中验证辅助性.
- 使用淘汰小鼠和间隙结合抑制剂,研究膜上皮细胞 (AEC) 和STING信号的作用.
主要成果:
- 在小鼠中,PS- GAMP显著增强了流感疫苗诱导的幽默和CD8+ T细胞免疫反应.
- 用PS- GAMP辅助的H1N1疫苗进行鼻腔免疫,至少在6个月内诱导对H1N1,H3N2,H5N1和H7N9病毒的强烈交叉保护.
- 肺内存的CD8+T细胞得到维持.
- 在鱼中证实了辅助作用.
- 通过PS-GAMP介导的辅助性取决于AEC和功能间隙结的STING表达.
结论:
- 通过模仿早期病毒感染而没有过度炎症,PS- GAMP作为一种强大的辅助剂,增强了疫苗诱导的免疫力.
- 在PS-GAMP诱导的异型亚型免疫中,AEC起着至关重要的作用.
- 这种新型辅助剂策略有望开发具有广泛和持久交叉保护的下一代流感疫苗.
更多相关视频
10:39Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
13.1K
08:10Production of High-Titer Infectious Influenza Pseudotyped Particles with Envelope Glycoproteins from Highly Pathogenic H5N1 and Avian H7N9 Viruses
Published on: January 15, 2020
8.8K
相关概念视频
01:27Influenza
Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
01:25Inhibitors Of Virion Release
Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...