Increased efficacy of a trivalent nicotine vaccine compared to a dose-matched monovalent vaccine when formulated with alum
Increased efficacy of a trivalent nicotine vaccine compared to a dose-matched monovalent vaccine when formulated with alum
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DOI：
10.1016/j.vaccine.2013.10.051
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发表时间：
2013-12-16
期刊：
影响因子：
5.5
通讯作者：
Pentel, Paul R.
中科院分区：
文献类型：
--
作者：
de Villiers, Sabina H. L.;Cornish, Katherine E.;Pentel, Paul R.
针对尼古丁的疫苗是一种潜在的治疗吸烟的方法。临床试验表明，只有在高抗体应答者中才有效;因此，有必要提高尼古丁疫苗的有效性。使用激活几个B细胞群的多价疫苗是增加抗体应答的可能方法。本研究的目的是研究是否可以混合三种不同的尼古丁免疫原以产生独立的反应，从而产生相加的抗体滴度，以及这是否会比单价疫苗产生的抗体更大程度地改变尼古丁分布。当免疫原被s.c.与同等剂量的单价疫苗相比，使用明矾佐剂的三价疫苗产生显著更高的滴度，并在更大程度上防止静脉内尼古丁剂量分布到脑中。与单价组相比，三价组中抗体滴度>1：10，000的大鼠数量显著增加。三价疫苗中不同尼古丁免疫原产生的滴度之间没有相关性，支持免疫原从不同的B细胞群体产生独立应答的假设。相反，当在弗氏佐剂中腹膜内给药时，三价尼古丁疫苗的免疫原性并不比其组分单价疫苗高。与单独的单价疫苗相比，如果将未缀合的蛋白质加入到在弗氏佐剂中配制的单价疫苗中，则疫苗免疫原性被抑制。这些数据表明蛋白质蛋白质相互作用对滴度产生负面影响，并且当疫苗与弗氏佐剂一起配制时是明显的。总之，用明矾配制的三价尼古丁疫苗显示出比剂量匹配的单价疫苗显著更高的效力，并且可以提供增加尼古丁疫苗免疫原性的策略。这种方法可以推广到其他尼古丁免疫原或其他成瘾药物的疫苗。(C)2013爱思唯尔有限公司保留所有权利。
Vaccination against nicotine is a potential treatment for tobacco smoking. Clinical trials show effect only in high antibody responders; therefore it is necessary to increase the effectiveness of nicotine vaccines. The use of a multivalent vaccine that activates several B cell populations is a possible approach to increase antibody response. The aim of this study was to investigate whether three different nicotine immunogens could be mixed to generate independent responses resulting in additive antibody titers, and whether this would alter nicotine distribution to a greater extent than antibodies generated by a monovalent vaccine. When immunogens were administered s.c. with alum adjuvant, the trivalent vaccine generated significantly higher titers and prevented the distribution of an i.v. nicotine dose to brain to a greater extent than an equivalent dose of a monovalent vaccine. The number of rats with antibody titers >1:10,000 was significantly increased in the trivalent group compared to the monovalent group. There were no correlations between the titers generated by the different nicotine immunogens in the trivalent vaccine, supporting the hypothesis that the immunogens generated independent responses from distinct populations of B cells. In contrast, when administered i.p. in Freund's adjuvant, the trivalent nicotine vaccine was not more immunogenic than its component monovalent vaccine. Vaccine immunogenicity was suppressed if unconjugated protein was added to the monovalent vaccine formulated in Freund's adjuvant, compared to monovalent vaccine alone. These data suggest a protein protein interaction that affects titers negatively and is apparent when the vaccines are formulated with Freund's adjuvant. In summary, a trivalent nicotine vaccine formulated with alum showed significantly higher efficacy than a dose-matched monovalent vaccine and may offer a strategy for increasing nicotine vaccine immunogenicity. This approach may be generalizable to other nicotine immunogens or vaccines for other addictive drugs. (C) 2013 Elsevier Ltd. All rights reserved.