佐剂刺激 TLR3 或 NLPR3 通路可提高流感样病毒颗粒疫苗在老年小鼠中的效率。
Adjuvants that stimulate TLR3 or NLPR3 pathways enhance the efficiency of influenza virus-like particle vaccines in aged mice.
机构信息
Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
出版信息
Vaccine. 2011 Nov 8;29(48):9081-92. doi: 10.1016/j.vaccine.2011.09.051. Epub 2011 Sep 28.
There is intense interest in the design and use of vaccine strategies against influenza to enhance protective immune responses in the elderly. To address the need for improved influenza vaccines for the aged, two inflammatory adjuvants, Imject(®) alum (a stimulator of the Nod-like receptor, Nalp3) and poly I:C (a toll-like receptor type 3 ligand), were used during vaccination with novel influenza virus-like particles (VLP). Adult (4 month old) or aged (24 month old) mice were vaccinated with VLPs alone or in combination with adjuvant. VLP-vaccinated adult mice were protected from a lethal influenza virus challenge without the use of either adjuvant. In contrast, only aged mice that were vaccinated with VLPs plus adjuvant survived challenge, whereas ∼33% of the mice vaccinated with VLP only survived challenge. Mice vaccinated with adjuvant only did not survive challenge despite similar levels of activation of CD11b(+)/CD11c(+) dendritic cells in the lungs. The protection was not associated with HAI titers or HA specific CD8(+) T cells, since both adjuvants boosted the VLP-induced serum HAI titers and CD8(+) responses in adult mice, but not aged mice. Influenza VLPs used in combination with two different inflammatory adjuvants during vaccination allow for the immune system to overcome the deficiency in the aged immune system to influenza virus infection.
人们对设计和使用流感疫苗策略非常感兴趣,旨在增强老年人的保护性免疫反应。为了解决老年人流感疫苗改进的需求,在新型流感病毒样颗粒(VLP)接种期间使用了两种炎症佐剂,Imject(®)明矾(Nod 样受体,Nalp3 的刺激剂)和聚 I:C(一种 Toll 样受体 3 配体)。成年(4 月龄)或老年(24 月龄)小鼠单独或联合佐剂接种 VLP。VLP 疫苗接种的成年小鼠在不使用佐剂的情况下免受致死性流感病毒攻击的保护。相比之下,只有接种了 VLP 加佐剂的老年小鼠才能在挑战中存活,而仅接种了 VLP 的小鼠中约有 33%存活下来。尽管肺部的 CD11b(+)/CD11c(+)树突状细胞的激活水平相似,但仅接种佐剂的小鼠在挑战中无法存活。这种保护与 HAI 滴度或 HA 特异性 CD8(+)T 细胞无关,因为两种佐剂均增强了成年小鼠中 VLP 诱导的血清 HAI 滴度和 CD8(+)反应,但对老年小鼠没有。在接种疫苗时,流感 VLP 与两种不同的炎症佐剂联合使用,可以使免疫系统克服老年人群对流感病毒感染的免疫缺陷。