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Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction
Biomaterials ( IF 14.0 ) Pub Date : 2017-11-20 , DOI: 10.1016/j.biomaterials.2017.11.021
Zongmin Zhao , Brian Harris , Yun Hu , Theresa Harmon , Paul R. Pentel , Marion Ehrich , Chenming Zhang

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.



中文翻译:

将分子佐剂合理掺入基于纳米颗粒的混合尼古丁疫苗中,以进行尼古丁成瘾的免疫治疗

由于其低免疫原性,当前临床测试的尼古丁疫苗尚未显示出增强的戒烟功效。实现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。这项研究旨在通过合理掺入基于收费样受体(TLR)的佐剂,包括单磷酰脂质A(MPLA),雷西莫德(R848),CpG寡脱氧核苷酸1826(CpG ODN 1826),促进基于纳米颗粒的尼古丁杂种疫苗的免疫原性。 ,以及它们的组合。发现与游离对应物相比,树突状细胞更有效地吸收了递送纳米颗粒的模型佐剂。细胞内化后,纳米疫苗颗粒被转运至内体区室。掺入单或双TLR佐剂不仅大大增加了总抗尼古丁IgG滴度,而且还显着影响了小鼠中IgG亚型的分布。特别是,携带MPLA + R848或MPLA + ODN 1826的纳米疫苗产生的抗尼古丁抗体效价比不携带一种或一种佐剂的纳米疫苗高得多。同时,用MPLA + R848佐剂的纳米疫苗诱导的抗尼古丁抗体具有比携带MPLA + ODN 1826的纳米疫苗所诱导的抗烟碱抗体显着更高的亲和力。此外,所有选择的TLR佐剂(MPLA除外)的掺入都会减少大脑尼古丁激发后小鼠中的尼古丁水平。特别是,带有MPLA + R848的纳米疫苗显示出降低进入大脑的尼古丁水平的最佳能力。总的来说,

更新日期:2017-11-21
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