Mucosal Administration of Cycle-Di-Nucleotide-Adjuvanted Virosomes Efficiently Induces Protection against Influenza H5N1 in Mice.
Mucosal Administration of Cycle-Di-Nucleotide-Adjuvanted Virosomes Efficiently Induces Protection against Influenza H5N1 in Mice.
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DOI：
10.3389/fimmu.2017.01223
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发表时间：
2017
影响因子：
7.3
通讯作者：
Guzmán CA
中科院分区：
文献类型：
--
作者：
Ebensen T;Debarry J;Pedersen GK;Blazejewska P;Weissmann S;Schulze K;McCullough KC;Cox RJ;Guzmán CA
新的流感毒株的出现突显了对更有效的流感疫苗的需求，这可能会导致新的大流行。有越来越多的易感人群面临流感严重并发症的风险，例如老年人，他们只受到目前获得许可的季节性疫苗的部分保护。改进季节性和大流行疫苗的一种策略是利用佐剂来增强和调节诱发的免疫反应。在这项研究中，我们检测了最近描述的佐剂环状单磷酸腺苷(c-di-AMP)作为改进的粘膜流感疫苗的佐剂的能力，并诱导对H5N1流感的有效保护。具体而言，c-di-AMP可促进(1)有效的局部和全身体液免疫反应，包括保护性血凝抑制滴度；(2)有效的细胞反应，包括多功能T细胞活性；(3)诱导持久免疫；(4)保护免受病毒攻击。此外，我们证明了佐剂的剂量节约能力以及激发跨分支保护性免疫反应的能力。总体而言，我们的结果表明，c-di-AMP有助于产生有效接种流感疫苗所需的保护性细胞介导的免疫反应，这支持了c-di-AMP作为季节性和大流行性流感黏膜疫苗的佐剂的进一步发展。
The need for more effective influenza vaccines is highlighted by the emergence of novel influenza strains, which can lead to new pandemics. There is a growing population of susceptible subjects at risk for severe complications of influenza, such as the elderly who are only in part protected by current licensed seasonal vaccines. One strategy for improving seasonal and pandemic vaccines takes advantage of adjuvants to boost and modulate evoked immune responses. In this study, we examined the capacity of the recently described adjuvant cyclic di-adenosine monophosphate (c-di-AMP) to serve as an adjuvant for improved mucosal influenza vaccines, and induce effective protection against influenza H5N1. In detail, c-di-AMP promoted (i) effective local and systemic humoral immune responses, including protective hemagglutination inhibition titers, (ii) effective cellular responses, including multifunctional T cell activity, (iii) induction of long-lasting immunity, and (iv) protection against viral challenge. Furthermore, we demonstrated the dose-sparing capacity of the adjuvant as well as the ability to evoke cross-clade protective immune responses. Overall, our results suggest that c-di-AMP contributes to the generation of a protective cell-mediated immune response required for efficacious vaccination against influenza, which supports the further development of c-di-AMP as an adjuvant for seasonal and pandemic influenza mucosal vaccines.
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影响因子：
6.7
作者：
Kara EE;Comerford I;Fenix KA;Bastow CR;Gregor CE;McKenzie DR;McColl SR
通讯作者：
McColl SR
影响因子：
3.7
作者：
Lewis DJ;Huo Z;Barnett S;Kromann I;Giemza R;Galiza E;Woodrow M;Thierry-Carstensen B;Andersen P;Novicki D;Del Giudice G;Rappuoli R
通讯作者：
Rappuoli R
DOI：
10.1084/jem.20011910
发表时间：
2002-01-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lamm ME;Phillips-Quagliata JM
通讯作者：
Phillips-Quagliata JM
影响因子：
5.4
作者：
Guo, Hailong;Santiago, Felix;Topham, David J.
通讯作者：
Topham, David J.
影响因子：
5.5
作者：
Libanova, Rimma;Ebensen, Thomas;Guzman, Carlos A.
通讯作者：
Guzman, Carlos A.