Adjuvants for vaccines to drugs of abuse and addiction.
Adjuvants for vaccines to drugs of abuse and addiction.
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DOI：
10.1016/j.vaccine.2014.07.085
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发表时间：
2014-09-22
期刊：
影响因子：
5.5
通讯作者：
Beck, Zoltan
中科院分区：
文献类型：
--
作者：
Alving, Carl R.;Matyas, Gary R.;Torres, Oscar;Jalah, Rashmi;Beck, Zoltan
关键词：
正在开发针对滥用药物的免疫治疗性疫苗，包括尼古丁、可卡因、海洛因、羟考酮、甲基苯丙胺和其他药物。这种疫苗的理论基础是诱导抗体，以抗体结合药物的形式将药物隔离在血液中，这种药物无法穿过血脑屏障，从而防止精神活性影响。因为药物是半抗原，所以成功的疫苗依赖于开发合适的半抗原-蛋白质载体结合物。然而，由于有效的疫苗需要诱导高水平和长时间的抗体，而且注射滥用的T非依赖性半抗原药物不会诱导记忆回忆反应，因此佐剂在免疫过程中起着关键作用。如本文所述，临床前研究经常使用强佐剂，如完全和不完全弗氏佐剂，以及其他不能或在许多较新的佐剂的情况下从未用于人类的佐剂。除此之外，在人类临床试验中，尼古丁和可卡因的候选疫苗中唯一包括的佐剂是氢氧化铝凝胶。虽然铝盐已被广泛用于世界各地的许多已获许可的疫苗，但人类对铝盐佐剂疫苗对滥用半抗原药物的反应的经验表明，免疫反应太弱，无法开发成功的疫苗。需要的是一种安全、有效、可广泛获得、易于制造和成本效益高的佐剂或佐剂组合。基于我们对该领域的回顾，我们推荐用于研究或产品开发的以下佐剂组合：吸附了单磷脂A的铝盐；含有单磷脂A的脂质体[L(M解放军)]；吸附在铝盐上的L(MPLA)；水包油乳剂；或含有MPLA的水包油乳剂。
Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA.
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