Heroin vaccine: Using titer, affinity, and antinociception as metrics when examining sex and strain differences
Heroin vaccine: Using titer, affinity, and antinociception as metrics when examining sex and strain differences
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DOI：
10.1016/j.vaccine.2019.05.061
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发表时间：
2019-07-09
期刊：
影响因子：
5.5
通讯作者：
Janda, Kim D.
中科院分区：
文献类型：
--
作者：
Hwang, Candy S.;Smith, Lauren C.;Janda, Kim D.
禁毒疫苗有可能成为对抗物质使用障碍（SUD）的新干预措施。然而，鉴于迄今为止SUD疫苗试验中个体间变异性的挑战，新的干预措施应确保在不同人群中产生强大的免疫应答和安全性。这需要考虑到性别和遗传基因差异对滥用物质和疫苗本身的反应。为了测试对我们的海洛因-破伤风类毒素（Her-TT）免疫缀合物疫苗的应答变异性，我们接种了来自几种小鼠品系的雄性和雌性小鼠，包括Swiss韦伯斯特（SW）、BALB/c和杰克逊多样性小鼠（J：DO）。先前对接种疫苗的雄性SW小鼠进行的研究表明，一种罕见的超敏反应导致小鼠在暴露于低剂量海洛因后迅速死亡。我们的研究结果表明，这种反应仅限于雄性SW小鼠，而不是任何其他品系或雌性SW小鼠。我们的数据表明，这种超敏反应不是过度活跃的细胞因子或IgE反应的结果。接种疫苗是类似的有效性之间的性别为每种菌株和对重复的海洛因挑战。在抗伤害感受行为试验中，近交系BALB/c和J：DO小鼠对海洛因的免疫应答最好。这些结果强调了在测试新的SUD疫苗时，将男性和女性受试者与不同菌株一起沿着以模拟不同人群的重要性。(C)2019爱思唯尔有限公司版权所有。
Anti-drug vaccines have potential as new interventions against substance use disorder (SUD). However, given the challenges seen with inter-individual variability in SUD vaccine trials to date, new interventions should ensure a robust immune response and safety profile among a diverse population. This requires accounting for sex and heritable genetic differences in response to both abused substances as well as the vaccination itself. To test response variability to our heroin-tetanus toxoid (Her-TT) immunoconjugate vaccine, we vaccinated male and female mice from several mouse strains including Swiss Webster (SW), BALB/c, and Jackson diversity mice (J:DO). Previous studies with vaccinated male SW mice demonstrated a rare hypersensitivity resulting in mice rapidly expiring with exposure to a low dose of heroin. Our results indicate that this response is limited to only male SW mice, and not to any other strain or female SW mice. Our data suggest that this hypersensitivity is not the result of an overactive cytokine or IgE response. Vaccination was similarly effective among the sexes for each strain and against repeated heroin challenge. Inbred BALB/c and J:DO mice were found to have the best vaccine response against heroin in antinociception behavioral assay. These results highlight the importance of incorporating both male and female subjects, along with different strains to mimic diverse human populations, as new SUD vaccines are being tested. (C) 2019 Elsevier Ltd. All rights reserved.