New Directions in Nicotine Vaccine Design and Use
New Directions in Nicotine Vaccine Design and Use
复制标题
DOI：
10.1016/b978-0-12-420118-7.00014-7
复制
发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
LeSage, Mark G.
中科院分区：
文献类型：
--
作者：
Pentel, Paul R.;LeSage, Mark G.
尼古丁疫苗的临床试验表明，它们可以提高戒烟率，但不能可靠地产生所需的持续高血清抗体浓度。正在评估一系列广泛的下一代策略，以增强疫苗功效或通过其他机制提供抗体。蛋白质缀合物疫苗可以通过半抗原或接头设计的修改或通过优化半抗原密度来改进。将半抗原与病毒样颗粒或破坏的病毒缀合可以允许利用与高免疫原性相关的天然存在的病毒特征。利用尼古丁上不同接头位置的缀合物可以充当独立的免疫原，因此组合使用它们产生的抗体浓度比单一免疫原产生的抗体浓度更高。纳米颗粒疫苗由半抗原、T 细胞辅助肽和附着在脂质体或合成支架上的佐剂组成，目前正处于开发的早期阶段。纳米颗粒疫苗提供了对疫苗成分化学计量和间距以及免疫原大小和形状进行精确和一致控制的可能性。尼古丁特异性单克隆抗体的被动转移可以更好地控制抗体剂量，能够提供非常高的剂量，并且可以立即起效，但价格昂贵且作用持续时间比疫苗短。病毒载体介导的抗体生产基因转移可以在动物中引起高水平的抗体表达，并且如果证实这种方法的长期安全性，则可以提供疫苗接种或被动免疫的替代方案。下一代免疫疗法可能比第一代疫苗更有效。
Clinical trials of nicotine vaccines suggest that they can enhance smoking cessation rates but do not reliably produce the consistently high serum antibody concentrations required. A wide array of next-generation strategies are being evaluated to enhance vaccine efficacy or provide antibody through other mechanisms. Protein conjugate vaccines may be improved by modifications of hapten or linker design or by optimizing hapten density. Conjugating hapten to viruslike particles or disrupted virus may allow exploitation of naturally occurring viral features associated with high immunogenicity. Conjugates that utilize different linker positions on nicotine can function as independent immunogens, so that using them in combination generates higher antibody concentrations than can be produced by a single immunogen. Nanoparticle vaccines, consisting of hapten, T cell help peptides, and adjuvants attached to a liposome or synthetic scaffold, are in the early stages of development. Nanoparticle vaccines offer the possibility of obtaining precise and consistent control of vaccine component stoichiometry and spacing and immunogen size and shape. Passive transfer of nicotine-specific monoclonal antibodies offers a greater control of antibody dose, the ability to give very high doses, and an immediate onset of action but is expensive and has a shorter duration of action than vaccines. Viral vector-mediated transfer of genes for antibody production can elicit high levels of antibody expression in animals and may present an alternative to vaccination or passive immunization if the long-term safety of this approach is confirmed. Next-generation immunotherapies are likely to be substantially more effective than first-generation vaccines.