The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.
The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.
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DOI：
10.4049/jimmunol.1500385
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发表时间：
2015-06-15
期刊：
影响因子：
--
通讯作者：
Pravetoni M
中科院分区：
文献类型：
--
作者：
Laudenbach M;Baruffaldi F;Vervacke JS;Distefano MD;Titcombe PJ;Mueller DL;Tubo NJ;Griffith TS;Pravetoni M
用于成瘾、癌症或其他慢性非传染性疾病的治疗性疫苗的转化一直很缓慢，因为只有一小部分免疫受试者达到了有效的抗体水平。我们假设，个体幼稚和早期激活的半抗原特异性B细胞数量的差异决定了疫苗接种后血清抗体水平和疫苗效力。使用针对高度滥用的处方阿片样物质羟考酮的模型疫苗，通过流式细胞术与基于抗原的磁性富集配对来分析对基于羟考酮的半抗原（6OXY）特异性的多克隆B细胞群。免疫前后，脾活检或血液中6 OXY特异性B细胞的频率较高，与随后较高的羟考酮特异性血清抗体滴度及其阻断羟考酮向脑分布和羟考酮诱导的小鼠行为的效力相关。6OXY特异性B细胞活化和疫苗效力的大小与CD4+ T细胞群体的大小密切相关。富集的6OXY特异性B细胞的频率在各种小鼠组织中是一致的。这些数据提供了新的证据，表明初始或早期激活的疫苗特异性B和T细胞频率的变化可以解释个体对疫苗的反应，并可能预测治疗性疫苗的临床疗效。
Translation of therapeutic vaccines for addiction, cancer or other chronic non-communicable diseases has been slow because only a small subset of immunized subjects achieved effective antibody levels. We hypothesize that individual variability in the number of naïve and early-activated hapten-specific B cells determines post-vaccination serum antibody levels and vaccine efficacy. Using a model vaccine against the highly abused prescription opioid oxycodone, the polyclonal B cell population specific for an oxycodone-based hapten (6OXY) was analyzed by flow cytometry paired with antigen-based magnetic enrichment. A higher frequency of 6OXY-specific B cells in either spleen biopsies or blood, before and after immunization, correlated to subsequent greater oxycodone-specific serum antibody titers and their efficacy in blocking oxycodone distribution to the brain and oxycodone-induced behavior in mice. The magnitude of 6OXY-specific B cell activation and vaccine efficacy was tightly correlated to the size of the CD4+ T cell population. The frequency of enriched 6OXY-specific B cells was consistent across various mouse tissues. These data provide novel evidence that variations in the frequency of naïve or early-activated vaccine-specific B and T cells can account for individual responses to vaccines and may predict the clinical efficacy of a therapeutic vaccine.
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影响因子：
6.7
作者：
Dileepan T;Linehan JL;Moon JJ;Pepper M;Jenkins MK;Cleary PP
通讯作者：
Cleary PP
影响因子：
7.3
作者：
Pravetoni, Marco;Le Naour, Morgan;Tucker, Ashli M.;Harmon, Theresa M.;Hawley, Tara M.;Portoghese, Philip S.;Pentel, Paul R.
通讯作者：
Pentel, Paul R.
影响因子：
11.5
作者：
Gilewski, Teresa A.;Ragupathi, Govind;Livingston, Philip O.
通讯作者：
Livingston, Philip O.
DOI：
10.1126/science.1201730
发表时间：
2011-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Pape KA;Taylor JJ;Maul RW;Gearhart PJ;Jenkins MK
通讯作者：
Jenkins MK
影响因子：
4.4
作者：
Frasca, Daniela;Diaz, Alain;Blomberg, Bonnie B.
通讯作者：
Blomberg, Bonnie B.