Suppression of nicotine-induced pathophysiology by an adenovirus hexon-based antinicotine vaccine.
Suppression of nicotine-induced pathophysiology by an adenovirus hexon-based antinicotine vaccine.
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通过基于腺病毒六邻体的抗尼古丁疫苗抑制尼古丁诱导的病理生理学。
DOI：
10.1089/hum.2012.245
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发表时间：
2013
影响因子：
4.2
通讯作者：
Crystal,RonaldG
中科院分区：
文献类型：
--
作者：
Rosenberg,JonathanB;De,BishnuP;Hicks,MartinJ;Janda,KimD;Kaminsky,StephenM;Worgall,Stefan;Crystal,RonaldG
尽管开展了禁烟运动，吸烟仍然是一种具有重大社会影响的普遍成瘾，占死亡人数的五分之一。帮助吸烟者戒烟的戒烟疗法效果不佳，复发率很高。鉴于尼古丁是香烟的主要成瘾物质，我们基于从血清5型腺病毒(Ad)衣壳中提纯的六邻体蛋白的高度免疫原性，开发了一种戒烟疫苗。我们推测，一种有效的抗烟碱疫苗可能是基于将尼古丁半抗原AM1偶联到纯化的Ad Hexon蛋白上。为了评估这一点，将AM1与从血清5Ad提纯的六邻体偶联，以生产HexonAM1疫苗。C57BL/6小鼠每日皮下注射尼古丁0.5 mg/kg致敏，造成尼古丁成瘾。对照组用磷酸盐缓冲盐水(PBS)致敏。然后在0、3和6周用HexonAM1(4 μg，肌肉注射)免疫小鼠。6周后，HexonAM1免疫组小鼠血清抗烟碱抗体效价为1.1×106±7.6×104。为了证明这些高抗烟碱效价足以抑制尼古丁的影响，HexonAM1疫苗接种的小鼠在5周内接受尼古丁攻击(0.5 mg/kg wt)，以评估尼古丁诱导的低活动行为。在所有挑战中，接种HexonAM1疫苗的小鼠的行为与PBS挑战的幼稚小鼠相似。这些数据表明，由尼古丁类似物与Ad Hexon偶联组成的疫苗可以激发高水平的抗烟碱抗体，足以抑制尼古丁诱导的行为。HexonAM1疫苗代表了针对小分子的疫苗的平台范例。
Despite antismoking campaigns, cigarette smoking remains a pervasive addiction with significant societal impact, accounting for one of every five deaths. Smoking cessation therapies to help smokers quit are ineffective with a high recidivism rate. With the knowledge that nicotine is the principal addictive compound of cigarettes, we have developed an antismoking vaccine based on the highly immunogenic properties of the hexon protein purified from the serotype 5 adenovirus (Ad) capsid. We hypothesized that an effective antinicotine vaccine could be based on coupling the nicotine hapten AM1 to purified Ad hexon protein. To assess this, AM1 was conjugated to hexon purified from serotype 5 Ad to produce the HexonAM1 vaccine. C57Bl/6 mice were sensitized by 10 daily nicotine administrations (0.5 mg/kg, subcutaneous) to render the mice addicted to nicotine. Control groups were sensitized to phosphate-buffered saline (PBS). The mice were then immunized with HexonAM1 (4 μg, intramuscular) at 0, 3, and 6 weeks. By 6 weeks, the HexonAM1-vaccinated mice had serum antinicotine antibody titers of 1.1×106±7.6×104. To demonstrate that these high antinicotine titers were sufficient to suppress the effects of nicotine, HexonAM1-vaccinated mice were evaluated for nicotine-induced hypoactive behavior with nicotine challenges (0.5 mg/kg wt) over 5 weeks. In all challenges, the HexonAM1-vaccinated mice behaved similar to PBS-challenged naive mice. These data demonstrate that a vaccine comprised of a nicotine analog coupled to Ad hexon can evoke a high level of antinicotine antibodies sufficient to inhibit nicotine-induced behavior. The HexonAM1 vaccine represents a platform paradigm for vaccines against small molecules.