Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine.
Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine.
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DOI：
10.1016/j.vaccine.2014.01.028
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发表时间：
2014-03-14
期刊：
影响因子：
5.5
通讯作者：
Alving, Carl R.
中科院分区：
文献类型：
--
作者：
Matyas, Gary R.;Rice, Kenner C.;Cheng, Kejun;Li, Fuying;Antoline, Joshua F. G.;Iyer, Malliga R.;Jacobson, Arthur E.;Mayorov, Alexander V.;Beck, Zoltan;Torres, Oscar B.;Alving, Carl R.
关键词：
新的合成化合物类似于海洛因及其主要活性代谢产物，6-乙酰吗啡和吗啡，作为潜在的替代半抗原的能力，接口与免疫系统的海洛因疫苗进行了检查。最近的研究表明，海洛因样半抗原必须水解降解，以诱导对海洛因和代谢物的独立免疫反应，导致含有抗体混合物的抗血清（2型交叉反应）。为了测试这一概念，两个独特的水解稳定的半抗原的基础上推定的结构面部相似性海洛因或其活性代谢产物。在将海洛因样半抗原（DiAmHap）缀合至破伤风类毒素并与含有单磷酰脂质A的脂质体混合后，在小鼠中两次注射后的高滴度抗体具有互补结合位点，其表现出与海洛因及其两种生理活性代谢物的强的1型（“真”）特异性交叉反应性。每种替代半抗原免疫的小鼠表现出减少的抗伤害性作用所造成的注射海洛因。这种方法避免了需要创建水解不稳定的合成海洛因样化合物，以诱导对海洛因及其活性代谢物的独立免疫应答，用于疫苗开发。通过抗体对水解稳定的替代半抗原的面部识别以及与海洛因及其代谢物的1型交叉反应性可以帮助指导合成化学策略以有效开发海洛因疫苗。
Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 (“true”) specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine.
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