Combining Active Immunization with Monoclonal Antibody Therapy To Facilitate Early Initiation of a Long-Acting Anti-Methamphetamine Antibody Response.
Combining Active Immunization with Monoclonal Antibody Therapy To Facilitate Early Initiation of a Long-Acting Anti-Methamphetamine Antibody Response.
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DOI：
10.1021/acs.jmedchem.5b00220
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发表时间：
2015-06-11
影响因子：
7.3
通讯作者：
Owens SM
中科院分区：
文献类型：
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作者：
Hambuchen MD;Carroll FI;Rüedi-Bettschen D;Hendrickson HP;Hennings LJ;Blough BE;Brieaddy LE;Pidaparthi RR;Owens SM
我们假设抗METH mAb可以与METH结合疫苗（MCV）联合使用，以安全地提高抗METH免疫应答的整体质量和强度。益处包括立即起效（来自mAb）、及时增加免疫应答（来自联合治疗）和持续数月的抗体应答持续时间（来自MCV）。合成了一种新的METH-like半抗原（METH-SSOO 9），然后将其与钥孔血蓝蛋白（ICKLH）的免疫蓝蛋白单体偶联以产生MCV，ICKLH-SOO 9。该疫苗与先前发现的抗METH mAb 7 F9组合，然后在大鼠中测试安全性和潜在功效。组合抗体疗法允许安全地实现早期高抗METH抗体应答，其在整个研究中持续存在。事实上，即使在四个月后，METH疫苗抗体仍然有能力显着降低0.56 mg/kg METH剂量引起的METH脑浓度。
We hypothesized that an anti-METH mAb could be used in combination with a METH-conjugate vaccine (MCV) to safely improve the overall quality and magnitude of the anti-METH immune response. The benefits would include immediate onset of action (from the mAb), timely increases in the immune responses (from the combined therapy) and duration of antibody response that could last for months (from the MCV). A novel METH-like hapten (METH-SSOO9) was synthesized and then conjugated to immunocyanin monomers of Keyhole limpet hemocyanin (ICKLH) to create the MCV, ICKLH-SOO9. The vaccine, in combination with previously discovered anti-METH mAb7F9, was then tested in rats for safety and potential efficacy. The combination antibody therapy allowed safe achievement of an early high anti-METH antibody response, which persisted throughout the study. Indeed, even after four months the METH vaccine antibodies still had the capacity to significantly reduce METH brain concentrations resulting from a 0.56 mg/kg METH dose.