Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines

Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines
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DOI:
10.1016/j.vaccine.2009.02.105
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发表时间:
2009-05-14
期刊:
影响因子:
5.5
通讯作者:
Sanderson, Sam D.
Sanderson, Sam D.
中科院分区:
医学3区
文献类型:
--
作者:
Duryee, Michael J.;Bevins, Rick A.;Sanderson, Sam D.

文献摘要

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通过将甲基半抗原(METH)共价连接到含有构象偏向的应答选择性分子佐剂YSFKPMPLaR(EP 54)的肽构建体来设计针对甲基苯丙胺(甲基)的疫苗。用含有EP 54的甲基疫苗免疫的大鼠产生对真实甲基的血清抗体滴度,这是改变甲基自我施用的免疫结果。免疫增加甲基自我管理表明药代动力学拮抗作用。免疫血清结合甲氨蝶呤修饰的靶蛋白的能力在甲氨蝶呤自我施用测定期间和之后不久显著降低,表明游离甲氨蝶呤的有效螯合。然而,免疫血清与MET修饰的靶蛋白的结合能力在无甲硫氨酸清除时间后34天恢复。(C)2009爱思唯尔有限公司保留所有权利。
Vaccines to methamphetamine (meth) were designed by covalently attaching a meth hapten (METH) to peptide constructs that contained a conformationally biased, response-selective molecular adjuvant, YSFKPMPLaR (EP54). Rats immunized with EP54-containing meth vaccines generated serum antibody titers to authentic meth, an immune outcome that altered meth self-administration. Immunization increased meth self-administration suggesting pharmacokinetic antagonism. The ability of immune sera to bind a METH-modified target protein dramatically decreased during and shortly after the meth self-administration assay, suggesting effective sequestration of free meth. However, the binding ability of immune sera to the METH-modified target protein was recovered 34 days after meth-free clearance time. (C) 2009 Elsevier Ltd. All rights reserved.