A Conjugate Vaccine Using Enantiopure Hapten Imparts Superior Nicotine-Binding Capacity

A Conjugate Vaccine Using Enantiopure Hapten Imparts Superior Nicotine-Binding Capacity
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DOI:
10.1021/jm501625j
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发表时间:
2015-01-22
影响因子:
7.3
通讯作者:
Janda, Kim D.
Janda, Kim D.
中科院分区:
医学1区
文献类型:
--
作者:
Lockner, Jonathan W.;Lively, Jenny M.;Janda, Kim D.

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一种领先的尼古丁缀合物疫苗仅对三分之一的临床试验参与者有效,可能部分是由于其使用外消旋尼古丁半抗原(+/-)-3 '-AmNic。用(+)-、(-)-或(+/-)-3 '-AmNic SucTT免疫雄性Wistar大鼠以及随后的抗体免疫测定表明,使用对映体纯的(-)-3'-AmNic半抗原的疫苗赋予结合(-)-尼古丁的上级能力。未来的尼古丁疫苗临床候选物必须结合这种设计考虑(即,半抗原对映体纯度)以使功效最大化。
A leading nicotine conjugate vaccine was only efficacious for one-third of clinical trial participants, likely due in part to its use of racemic nicotine hapten, (+/-)-3'-AmNic. Immunization of male Wistar rats with (+)-, (-)-, or (+/-)-3'-AmNicSucTT and subsequent antibody immunoassays suggest that a vaccine using enantiopure (-)-3'-AmNic hapten imparts superior capacity to bind (-)-nicotine. Future nicotine vaccine clinical candidates must incorporate this design consideration (i.e., hapten enantiopurity) in order to maximize efficacy.