Spontaneous Development of IgM Anti-Cocaine Antibodies in Habitual Cocaine Users: Effect on IgG Antibody Responses to a Cocaine Cholera Toxin B Conjugate Vaccine
Spontaneous Development of IgM Anti-Cocaine Antibodies in Habitual Cocaine Users: Effect on IgG Antibody Responses to a Cocaine Cholera Toxin B Conjugate Vaccine
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DOI：
10.1111/j.1521-0391.2013.00314.x
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发表时间：
2013-03-01
影响因子：
3.7
通讯作者：
Kosten, Thomas R.
中科院分区：
文献类型：
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作者：
Orson, Frank M.;Rossen, Roger D.;Kosten, Thomas R.
背景和目标 在可卡因疫苗研究中，只有少数受试者产生强烈的抗体反应。为了研究这个问题，在 IIb 期随机双盲安慰剂对照试验 (TA-CD 109) 中，测量了 55 名积极接种疫苗的受试者血清中对可卡因和霍乱毒素 B（CTB，用于增强对可卡因免疫反应的载体蛋白）的 IgG 和 IgM 抗体反应。方法 使用同种型特异性 ELISA 检测免疫前和免疫后间隔时间收集的系列样品中的 IgG 和 IgM 抗可卡因和抗 CTB 抗体。我们评估了接种前 IgM 抗可卡因抗体的患者的 IgG 抗可卡因反应。使用竞争性抑制ELISA来评估抗体特异性。结果和结论 在免疫接种前，36/55 名受试者可检测到可卡因 IgM 抗体，其中 9 名受试者的 IgM 水平高于 11μg/ml 的 95% 置信限。这 9 种药物在第 16 周时的 IgG 抗可卡因反应峰值显着降低，且均低于阻止娱乐性使用可卡因所必需的浓度 (40 克/毫升)。这些受试者的 IgG 抗 CTB 反应也有所降低。科学意义 在反复接触可卡因的娱乐性接触过程中，对可卡因产生 IgM 抗体反应的受试者，从可卡因结合疫苗中产生高水平 IgG 抗体的可能性显着降低。失败可能是由于娱乐性可卡因暴露诱导了 2 型 T 细胞独立免疫反应。这些人需要改进的疫苗，并且不适合使用当前可用的疫苗。 （Am J Addict 2013；22：169-174）
Background and Objectives In cocaine vaccine studies, only a minority of subjects made strong antibody responses. To investigate this issue, IgG and IgM antibody responses to cocaine and to cholera toxin B (CTBthe carrier protein used to enhance immune responses to cocaine) were measured in sera from the 55 actively vaccinated subjects in a Phase IIb randomized double-blind placebo-controlled trial (TA-CD 109). Methods Isotype specific ELISAs were used to measure IgG and IgM anti-cocaine and anti-CTB antibody in serial samples collected prior to and at intervals after immunization. We assessed IgG anti-cocaine responses of patients with pre-vaccination IgM anti-cocaine antibodies. Competitive inhibition ELISA was used to evaluate antibody specificity. Results and Conclusions Before immunization, 36/55 subjects had detectable IgM antibodies to cocaine, and 9 had IgM levels above the 95% confidence limit of 11g/ml. These nine had significantly reduced peak IgG anti-cocaine responses at 16 weeks, and all were below the concentration (40g/ml) considered necessary to discourage recreational cocaine use. The IgG anti-CTB responses of these same subjects were also reduced. Scientific Significance Subjects who develop an IgM antibody response to cocaine in the course of repeated recreational exposure to this drug are significantly less likely to produce high levels of IgG antibodies from the cocaine conjugate vaccine. The failure may be due to recreational cocaine exposure induction of a type 2 T-cell independent immune response. Such individuals will require improved vaccines and are poor candidates for the currently available vaccine. (Am J Addict 2013;22:169-174)