Novel Anti-Nicotine Vaccine Using a Trimeric Coiled-Coil Hapten Carrier.
Novel Anti-Nicotine Vaccine Using a Trimeric Coiled-Coil Hapten Carrier.
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新型抗雪Nicotine疫苗使用三聚体盘绕螺旋载体。
DOI：
10.1371/journal.pone.0114366
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Clegg CH
中科院分区：
文献类型：
--
作者：
Miller KD;Roque R;Clegg CH
烟草成瘾是世界上最大的公共卫生问题之一，是癌症和心脏病的主要原因，每年导致数百万人死亡。用于戒烟的疫苗在临床前模型中显示出相当大的前景，尽管在人体中诱导的功能性抗体应答在防止尼古丁进入大脑方面仅具有适度的有效性。产生具有大尼古丁结合能力的血清抗体的挑战是困难的，因为这种药物是非免疫原性的，必须作为半抗原缀合到蛋白载体上。为了克服传统载体如钥孔血蓝蛋白（KLH）的局限性，我们合成了短的三聚体卷曲螺旋肽（TCC），其产生一系列具有均匀化学计量和高密度的B和T细胞表位。在这里，我们比较了TCC-nic疫苗和两种对照KLH-nic疫苗的相对活性，所述对照KLH-nic疫苗使用明矾作为佐剂或GLA-SE，其含有配制在稳定的水包油乳液中的合成TLR 4激动剂。结果表明，通过抗尼古丁Ab滴度、亲和力和特异性测量，TCC的高半抗原密度与小鼠更好的免疫反应相关，并且导致抗载体免疫原性降低。用这种合成疫苗实现的Ab应答导致血清中的尼古丁结合能力，其可以阻止相当于三支吸烟香烟（0.05 mg/kg）的尼古丁剂量的>90%到达大脑。
Tobacco addiction represents one of the largest public health problems in the world and is the leading cause of cancer and heart disease, resulting in millions of deaths a year. Vaccines for smoking cessation have shown considerable promise in preclinical models, although functional antibody responses induced in humans are only modestly effective in preventing nicotine entry into the brain. The challenge in generating serum antibodies with a large nicotine binding capacity is made difficult by the fact that this drug is non-immunogenic and must be conjugated as a hapten to a protein carrier. To circumvent the limitations of traditional carriers like keyhole limpet hemocyanin (KLH), we have synthesized a short trimeric coiled-coil peptide (TCC) that creates a series of B and T cell epitopes with uniform stoichiometry and high density. Here we compared the relative activities of a TCC-nic vaccine and two control KLH-nic vaccines using Alum as an adjuvant or GLA-SE, which contains a synthetic TLR4 agonist formulated in a stable oil-in-water emulsion. The results showed that the TCC's high hapten density correlated with a better immune response in mice as measured by anti-nicotine Ab titer, affinity, and specificity, and was responsible for a reduction in anti-carrier immunogenicity. The Ab responses achieved with this synthetic vaccine resulted in a nicotine binding capacity in serum that could prevent >90% of a nicotine dose equivalent to three smoked cigarettes (0.05 mg/kg) from reaching the brain.
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影响因子：
3.7
作者：
Clegg CH;Roque R;Perrone LA;Rininger JA;Bowen R;Reed SG
通讯作者：
Reed SG
肽和蛋白质产生的化学方法。
DOI：
10.3390/molecules18044373
发表时间：
2013-04-12
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chandrudu S;Simerska P;Toth I
通讯作者：
Toth I
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.
影响因子：
5.5
作者：
Hu, Kun;Huang, Xuanyun;Yang, Xianle
通讯作者：
Yang, Xianle
影响因子：
4.7
作者：
Boylan, Nicholas J.;Zhou, Wen;Proos, Robert J.;Tolbert, Thomas J.;Wolfe, Janet L.;Laurence, Jennifer S.
通讯作者：
Laurence, Jennifer S.