Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría, Ciudad de México, México.
Laboratorio de Neurobiología Molecular y Neuroquímica de las Adicciones, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría, Ciudad de México, México.
Hum Vaccin Immunother. 2024 Dec 31;20(1):2299068. doi: 10.1080/21645515.2023.2299068. Epub 2024 Jan 16.
Vaccination active, promising alternative immunological strategy to treat of CUD. Various models of cocaine vaccines have been evaluated in animals and humans with relative success. In this sense, it is necessary to improve or optimize the cocaine vaccines already evaluated. Our laboratory previously reported the efficacy of the tetanus toxoid-conjugated morphine vaccine (M-TT). The M-TT vaccine can generate high titers of antibodies and reduce heroin-induced behavioral effects in rodents. So, it would be plausible to assume that if we modify the M-TT vaccine by changing the hapten and maintaining the rest of the structural elements of the vaccine, we will maintain the properties of the M-TT vaccine (high antibody titers). The objective of this study was to determine whether the antibodies generated by a tetanus toxoid-conjugated cocaine vaccine (COC-TT) can recognize and capture cocaine and decrease the cocaine-induced reinforcing effects. Male Wistar rats were immunized with the COC-TT. A solid-phase antibody-capture ELISA was used to monitor antibody titer responses after each booster dose in vaccinated animals. The study used cocaine self-administration and place-preference testing to evaluate the cocaine-reinforcing effects. The COC-TT vaccine could generate high levels of anti-cocaine antibodies. The antibodies reduced the cocaine self-administration and cocaine place preference. In addition, they decreased the cocaine-induced Fos protein expression. These findings suggest that the COC-TT vaccine generates a robust immunogenic response capable of reducing the reinforcing effects of cocaine, which supports its possible future use in clinical trials in patients with CUD.
疫苗接种是一种有前途的治疗可卡因使用障碍(CUD)的免疫策略。已经在动物和人类中评估了各种可卡因疫苗模型,取得了相对成功。在这方面,有必要改进或优化已经评估过的可卡因疫苗。我们的实验室之前报道了破伤风类毒素结合吗啡疫苗(M-TT)的功效。M-TT 疫苗可以产生高滴度的抗体,并减少啮齿动物中海洛因诱导的行为效应。因此,可以合理地假设,如果我们通过改变半抗原并保持疫苗的其余结构元件来修改 M-TT 疫苗,我们将保持 M-TT 疫苗的特性(高抗体滴度)。本研究的目的是确定破伤风类毒素结合可卡因疫苗(COC-TT)产生的抗体是否可以识别和捕获可卡因并减少可卡因诱导的强化作用。雄性 Wistar 大鼠用 COC-TT 免疫。在接种动物的每次加强剂量后,使用固相抗体捕获 ELISA 监测抗体滴度反应。该研究使用可卡因自我给药和位置偏好测试来评估可卡因的强化作用。COC-TT 疫苗可以产生高水平的抗可卡因抗体。这些抗体减少了可卡因的自我给药和可卡因的位置偏好。此外,它们还减少了可卡因诱导的 Fos 蛋白表达。这些发现表明,COC-TT 疫苗产生了强大的免疫反应能力,可以降低可卡因的强化作用,这支持了它在 CUD 患者临床试验中的未来可能应用。