Hybrid nanoparticle-based nicotine nanovaccines: Boosting the immunological efficacy by conjugation of potent carrier proteins.
Hybrid nanoparticle-based nicotine nanovaccines: Boosting the immunological efficacy by conjugation of potent carrier proteins.
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DOI：
10.1016/j.nano.2018.04.016
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Zhao Z;Hu Y;Harmon T;Pentel PR;Ehrich M;Zhang C
在这项工作中，通过缀合有效的载体蛋白候选物（匙孔血蓝蛋白（KLH）多聚体、KLH亚基、交叉反应性材料197（CRM 197）或破伤风类毒素（TT））来工程化一系列基于混合纳米颗粒的尼古丁纳米疫苗（NanoNicVac），以增强免疫功效。具有CRM197或TT的NanoNicVac比具有KLH多聚体或亚基的NanoNicVac更有效地被树突状细胞加工。携带CRM197或TT的NanoNicVac在小鼠中表现出比携带KLH多聚体或亚基的NanoNicVac显著更高的针对尼古丁的免疫原性和显著更低的针对载体蛋白的免疫原性。体内结果显示，NanoNicVac与CRM 197或TT在尼古丁激发后导致小鼠脑中尼古丁水平降低。所有研究结果表明，通过使用CRM197或TT代替KLH或KLH亚基作为载体蛋白，可以实现NanoNicVac增强的免疫功效，使NanoNicVac成为有希望的下一代抗尼古丁成瘾的免疫候选物。
A series of hybrid nanoparticle-based nicotine nanovaccines (NanoNicVac) were engineered in this work by conjugating potent carrier protein candidates (Keyhole limpet hemocyanin (KLH) multimer, KLH subunit, cross-reactive material 197 (CRM197), or tetanus toxoid (TT)) for enhanced immunological efficacy. NanoNicVac with CRM197 or TT were processed by dendritic cells more efficiently than that with KLH multimer or subunit. NanoNicVac carrying CRM197 or TT exhibited a significantly higher immunogenicity against nicotine and a considerably lower immunogenicity against carrier proteins than NanoNicVac carrying KLH multimer or subunit in mice. The in vivo results revealed that NanoNicVac with CRM197 or TT resulted in lower levels of nicotine in the brain of mice after nicotine challenge. All findings suggest that an enhanced immunological efficacy of NanoNicVac can be achieved by using CRM197 or TT instead of KLH or KLH subunit as carrier proteins, making NanoNicVac a promising next-generation immunotherapeutic candidate against nicotine addiction.
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