Targeted Phage Display-based Pulmonary Vaccination in Mice and Non-human Primates.
Targeted Phage Display-based Pulmonary Vaccination in Mice and Non-human Primates.
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基于靶向噬菌体展示的小鼠和非人类灵长类动物肺部疫苗接种。
DOI：
10.1016/j.medj.2020.10.005
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
Arap W
中科院分区：
文献类型：
--
作者：
Staquicini DI;Barbu EM;Zemans RL;Dray BK;Staquicini FI;Dogra P;Cardó-Vila M;Miranti CK;Baze WB;Villa LL;Kalil J;Sharma G;Prossnitz ER;Wang Z;Cristini V;Sidman RL;Berman AR;Panettieri RA Jr;Tuder RM;Pasqualini R;Arap W
广泛的肺泡毛细血管网络对于几种药物的给药是一个有吸引力的途径。一个关键的功能属性是，由于缺乏首过代谢，全身反应迅速开始。在这里，我们应用了一种组合方法，用于配体导向的肺部给药，作为疫苗接种中系统靶向的独特途径。我们在体内筛选了一个噬菌体展示随机肽库，以选择、鉴定和验证一个配体(CAKSMGDIVC)，该配体特异性地靶向并通过其受体α3β1整合素内化在肺气道和肺泡壁细胞表面，并在不影响肺内稳态的情况下介导CAKSMGDIVC-展示噬菌体结合和全身递送。作为概念验证，我们表明，在小鼠和非人类灵长类动物中，靶向CAKSMGDIVC展示噬菌体颗粒的肺部递送引发了系统性和特异性的体液反应。这一广泛的方法学蓝图代表了一个强大而通用的平台工具，使新的配体-受体发现具有许多潜在的翻译应用。癌症中心支持补助金授予德克萨斯大学M.D.安德森癌症中心(CA016672)、新墨西哥大学综合癌症中心(CA118100)、新泽西州罗格斯癌症研究所(CA072720)、吉尔森·隆格堡基金会颁发的研究奖项以及美国国立卫生研究院(NIH)授予的编号1R01CA226537。
The extensive alveolar capillary network of the lungs is an attractive route for administration of several agents. One key functional attribute is the rapid onset of systemic action due to the absence of first-pass metabolism. Here we applied a combinatorial approach for ligand-directed pulmonary delivery as a unique route for systemic targeting in vaccination. We screened a phage display random peptide library in vivo to select, identify, and validate a ligand (CAKSMGDIVC) that specifically targets and is internalized through its receptor, α3β1 integrin, on the surface of cells lining the lung airways and alveoli and mediates CAKSMGDIVC-displaying phage binding and systemic delivery without compromising lung homeostasis. As a proof-of-concept, we show that the pulmonary delivery of targeted CAKSMGDIVC-displaying phage particles in mice and non-human primates elicit a systemic and specific humoral response. This broad methodology blueprint represents a robust and versatile platform tool enabling new ligand-receptor discovery with many potential translational applications. Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center (CA016672), University of New Mexico Comprehensive Cancer Center (CA118100), Rutgers Cancer Institute of New Jersey (CA072720), research awards from the Gillson Longenbaugh Foundation, and National Institutes of Health (NIH) grant no. 1R01CA226537.
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影响因子：
16.6
作者：
Dogra P;Adolphi NL;Wang Z;Lin YS;Butler KS;Durfee PN;Croissant JG;Noureddine A;Coker EN;Bearer EL;Cristini V;Brinker CJ
通讯作者：
Brinker CJ
影响因子：
4.6
作者：
Brocato TA;Coker EN;Durfee PN;Lin YS;Townson J;Wyckoff EF;Cristini V;Brinker CJ;Wang Z
通讯作者：
Wang Z
DOI：
10.1165/rcmb.2017-0037ma
发表时间：
2017-11-01
影响因子：
6.4
作者：
Jansing, Nicole L.;McClendon, Jazalle;Zemans, Rachel L.
通讯作者：
Zemans, Rachel L.
影响因子：
11
作者：
Aghebati-Maleki L;Bakhshinejad B;Baradaran B;Motallebnezhad M;Aghebati-Maleki A;Nickho H;Yousefi M;Majidi J
通讯作者：
Majidi J
影响因子：
82.9
作者：
Dijkman, Karin;Sombroek, Claudia C.;Verreck, Frank A. W.
通讯作者：
Verreck, Frank A. W.