Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction.
Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction.
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DOI：
10.1016/j.biomaterials.2017.11.021
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发表时间：
2018-03
期刊：
影响因子：
14
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Zhao Z;Harris B;Hu Y;Harmon T;Pentel PR;Ehrich M;Zhang C
目前临床测试的尼古丁疫苗由于其低免疫原性而尚未显示出增强的戒烟功效。获得足够高的免疫原性是建立临床上可行的尼古丁疫苗的必要条件。本研究旨在通过合理地引入基于Toll样受体（TLR）的佐剂（包括单磷酰脂质A（MPLA）、Resiquimod（R848）、CpG寡脱氧核苷酸1826（CpG ODN 1826）及其组合）来促进基于混合纳米颗粒的尼古丁疫苗的免疫原性。发现纳米颗粒递送的模型佐剂比游离的对应物更有效地被树突状细胞吸收。纳米疫苗颗粒在细胞内化后转运至内体区室。单或双TLR佐剂的掺入不仅显著增加了总抗尼古丁IgG滴度，而且显著影响了小鼠中IgG亚型的分布。特别地，携带MPLA+R848或MPLA+ODN 1826的纳米疫苗产生比不携带或携带一种佐剂的纳米疫苗高得多的抗尼古丁抗体滴度。同时，由以MPLA+R848为佐剂的纳米疫苗引发的抗尼古丁抗体具有比由携带MPLA+ODN 1826的纳米疫苗引发的抗体显著更高的亲和力。此外，掺入所有选定的TLR佐剂（MPLA除外）降低了尼古丁激发后小鼠脑中的尼古丁水平。特别地，具有MPLA+R848的纳米疫苗表现出降低进入大脑的尼古丁水平的最佳能力。总的来说，TLR佐剂的合理掺入可以增强基于混合纳米颗粒的尼古丁疫苗的免疫功效，使其成为治疗尼古丁成瘾的有希望的下一代免疫候选物。
Current clinically-tested nicotine vaccines have yet shown enhanced smoking cessation efficacy due to their low immunogenicity. Achieving a sufficiently high immunogenicity is a necessity for establishing a clinically-viable nicotine vaccine. This study aims to facilitate the immunogenicity of a hybrid nanoparticle-based nicotine vaccine by rationally incorporating toll-like receptor (TLR)-based adjuvants, including monophosphoryl lipid A (MPLA), Resiquimod (R848), CpG oligodeoxynucleotide 1826 (CpG ODN 1826), and their combinations. The nanoparticle-delivered model adjuvant was found to be taken up more efficiently by dendritic cells than the free counterpart. Nanovaccine particles were transported to endosomal compartments upon cellular internalization. The incorporation of single or dual TLR adjuvants not only considerably increased total anti-nicotine IgG titers but also significantly affected IgG subtype distribution in mice. Particularly, the nanovaccines carrying MPLA+R848 or MPLA+ODN 1826 generated a much higher anti-nicotine antibody titer than those carrying none or one adjuvant. Meanwhile, the anti-nicotine antibody elicited by the nanovaccine adjuvanted with MPLA+R848 had a significantly higher affinity than that elicited by the nanovaccine carrying MPLA+ODN 1826. Moreover, the incorporation of all the selected TLR adjuvants (except MPLA) reduced the brain nicotine levels in mice after nicotine challenge. Particularly, the nanovaccine with MPLA+R848 exhibited the best ability to reduce the level of nicotine entering the brain. Collectively, rational incorporation of TLR adjuvants could enhance the immunological efficacy of the hybrid nanoparticle-based nicotine vaccine, making it a promising next-generation immunotherapeutic candidate for treating nicotine addiction.
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DOI：
10.1016/j.jconrel.2013.10.032
发表时间：
2014-01-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Li X;Aldayel AM;Cui Z
通讯作者：
Cui Z
影响因子：
10.8
作者：
Liu X;Xu Y;Yu T;Clifford C;Liu Y;Yan H;Chang Y
通讯作者：
Chang Y
影响因子：
56.9
作者：
Mata-Haro, Veronica;Cekic, Caglar;Mitchell, Thomas C.
通讯作者：
Mitchell, Thomas C.
影响因子：
5.5
作者：
Ilyinskii, Petr O.;Roy, Christopher J.;O'Neil, Conlin P.;Browning, Erica A.;Pittet, Lynnelle A.;Altreuter, David H.;Alexis, Frank;Tonti, Elena;Shi, Jinjun;Basto, Pamela A.;Iannacone, Matteo;Radovic-Moreno, Aleksandar F.;Langer, Robert S.;Farokhzad, Omid C.;von Andrian, Ulrich H.;Johnston, Lloyd P. M.;Kishimoto, Takashi Kei
通讯作者：
Kishimoto, Takashi Kei
影响因子：
5.5
作者：
de Villiers, Sabina H. L.;Cornish, Katherine E.;Pentel, Paul R.
通讯作者：
Pentel, Paul R.