Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine.
Active and Passive Immunization with an Anti-Methamphetamine Vaccine Attenuates the Behavioral and Cardiovascular Effects of Methamphetamine.
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DOI：
10.3390/vaccines10091508
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发表时间：
2022-09-09
期刊：
影响因子：
7.8
通讯作者：
Kosten TA
中科院分区：
文献类型：
--
作者：
Haile CN;Varner KJ;Huijing X;Arora R;Orson FM;Kosten TR;Kosten TA
背景：甲基苯丙胺使用障碍(MUD)是一个日益严重的健康问题，没有FDA批准的治疗方法。目前的一系列研究建立在我们之前开发MUD抗甲基苯丙胺(MA)疫苗的基础上。我们确定了一种包括吸附在氢氧化铝上的琥珀酸甲基苯丙胺(TT-SMA)的破伤风类毒素(TT-SMA)与新型Toll样受体-5激动剂entolimod联合使用的效果。方法：用TT-SMA+明矾和不同剂量的恩托莫特免疫小鼠(0、3、6周)，确定增强MA免疫原性的最佳剂量。然后，通过MA诱导的小鼠运动激活来评估功能效应。对疫苗产生的抗体进行被动免疫的实验，在MA诱导的雄性和雌性大鼠恢复药物复发的模型中，测试了其减弱MA诱导的心血管效应和改变MA的强化作用的能力。结果：TT-SMA+明矾联合恩托莫特(1、3、10µg)免疫10周后抗体水平达到高峰。在接种疫苗的小鼠和未接种疫苗的小鼠中，MA诱导的运动激活显着减弱，抗体水平与行走水平显著相关。被动免疫降低了雌雄大鼠服用MA后的平均动脉压，但不改变心率。被动免疫也减弱了MA恢复雄性和雌性大鼠已消失的寻药行为的能力。结果支持进一步开发该疫苗，用于预防MUD患者的复发。
Background: Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated to succinyl-methamphetamine (TT-SMA) adsorbed onto aluminum hydroxide (alum) in combination with the novel Toll-Like Receptor-5 agonist, entolimod. Methods: Mice were vaccinated (0, 3, 6 weeks) with TT-SMA+alum and various doses of entolimod to determine an optimal dose for enhancing immunogenicity against MA. Functional effects were then assessed using MA-induced locomotor activation in mice. Experiments using passive immunization of antibodies generated by the vaccine tested its ability to attenuate MA-induced cardiovascular effects and alter the reinforcing effects of MA in an MA-induced reinstatement of a drug seeking model of relapse in male and female rats. Results: Antibody levels peaked at 10 weeks following vaccination with TT-SMA+alum combined with entolimod (1, 3 and 10 µg). MA-induced locomotor activation was significantly attenuated in vaccinated vs. unvaccinated mice and antibody levels significantly correlated with ambulation levels. Passive immunization decreased mean arterial pressure following MA dosing in rats of both sexes but did not alter heart rate. Passive immunization also attenuated the ability of MA to reinstate extinguished drug-seeking behavior in male and female rats. Results support further development of this vaccine for relapse prevention for individuals with MUD.
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DOI：
10.1016/j.pbb.2010.12.004
发表时间：
2011-03
期刊：
Pharmacology, biochemistry, and behavior
影响因子：
--
作者：
Good RL;Radcliffe RA
通讯作者：
Radcliffe RA
影响因子：
7.3
作者：
Collins KC;Schlosburg JE;Bremer PT;Janda KD
通讯作者：
Janda KD
影响因子：
3.4
作者：
Kantak, KN;Collins, SL;Fox, BS
通讯作者：
Fox, BS
影响因子：
3.4
作者：
Keller, Courtney M.;Spence, Allyson L.;Goeder, Nicholas E. s
通讯作者：
Goeder, Nicholas E. s
DOI：
10.1039/c4cc00682h
发表时间：
2014-04-21
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Collins KC;Schlosburg JE;Lockner JW;Bremer PT;Ellis BA;Janda KD
通讯作者：
Janda KD