Preclinical development of a vaccine 'against smoking'
Preclinical development of a vaccine 'against smoking'
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DOI：
10.1159/000067433
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发表时间：
2002-10-01
期刊：
影响因子：
0.3
通讯作者：
Cerny, T
中科院分区：
文献类型：
--
作者：
Cerny, EH;Lévy, R;Cerny, T
背景：尼古丁是对烟草制品依赖的主要罪魁祸首，而烟草制品又是心血管疾病和癌症的主要病因。这份出版物描述了一种疫苗，它能诱导出针对尼古丁的抗体。血流中的抗体在尼古丁分子到达受体的途中拦截尼古丁分子，并在吸烟后不久极大地减少尼古丁流入大脑。方法：将尼古丁分子作为载体蛋白与霍乱毒素B化学偶联，诱导产生抗体。评估了皮下和鼻腔免疫后产生抗体的可能性。为了模拟真实条件，在接种疫苗前一周，在小鼠体内植入尼古丁泵，连续4周提供相当于5包香烟的尼古丁。疫苗的保护效果是在接种后5周通过比较接种和未接种的动物在攻击后5分钟内放射性标记尼古丁的流入与相当于2支香烟的尼古丁的量来衡量的。结果：该疫苗诱导的多克隆抗体的平均亲和力为1.80×10(7)L/摩尔。皮下免疫可产生较高水平的免疫球蛋白G类抗体，鼻腔免疫后小鼠唾液中可检测到较高水平的IgA抗体。在植入尼古丁泵的动物中，这种保护作用也是显著的：在未接种疫苗的动物的大脑中发现的放射性标记尼古丁中，只有不到10%可以在接种疫苗的动物的大脑中找到。结论：这些数据提供了可靠的证据，表明疫苗可以通过拦截尼古丁分子来打破吸烟和即时满足之间的恶性循环。令人惊讶的是，即使在极端条件下，也没有特定抗体耗尽的迹象，这使得吸烟者通过增加吸烟来克服疫苗的保护作用的可能性微乎其微。最后，1年后的高滴度特异性抗体让我们希望，可能只需隔几年就需要接种加强疫苗。
Background: Nicotine is the main culprit for dependence on tobacco-containing products, which in turn are a major etiologic factor for cardiovascular diseases and cancer. This publication describes a vaccine, which elicits antibodies against nicotine. The antibodies in the blood stream intercept the nicotine molecule on its way to its receptors and greatly diminish the nicotine influx to the brain shortly after smoking. Methods: The nicotine molecule is chemically linked to cholera toxin B as a carrier protein in order to induce antibodies. The potential to elicit antibodies after subcutaneous as well as intranasal immunization is evaluated. In order to simulate realistic conditions, nicotine pumps delivering the nicotine equivalent of 5 packages of cigarettes for 4 weeks are implanted into the mice 1 week prior to vaccination. The protective effect of the vaccine is measured 5 weeks after vaccination by comparing the influx of radiolabeled nicotine in the brains of vaccinated and non-vaccinated animals 5 min after challenge with the nicotine equivalent of 2 cigarettes. Results: The polyclonal antibodies induced by the vaccine show a mean avidity of 1.8 x 10(7) l/Mol. Subcutaneous immunization elicits high antibody levels of the IgG class, and significant IgA antibody levels in the saliva of vaccinated mice can be found after intranasal vaccination. The protective effect also in the animals with implanted nicotine pumps is significant: less than 10% of radiolabeled nicotine found in the brains of non-vaccinated animals can be found in the brains of vaccinated animals. Conclusions: These data provide credible evidence that a vaccine can break the vicious circle between smoking and instant gratification by intercepting the nicotine molecule. Astonishingly, there is no sign of exhaustion of specific antibodies even under extreme conditions, which makes it highly unlikely that a smoker can overcome the protective effect of the vaccine by smoking more. Finally, the high titers of specific antibodies after 1 year let us hope that booster vaccinations are probably only necessary in intervals of years.