Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Vaccine. 2014 Sep 22;32(42):5382-9. doi: 10.1016/j.vaccine.2014.07.085. Epub 2014 Aug 8.
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.
正在开发针对滥用药物（包括尼古丁、可卡因、海洛因、羟考酮、冰毒等）的免疫治疗疫苗。此类疫苗的理论基础是诱导抗体将血液中的药物结合形成抗体结合药物，使其无法穿过血脑屏障，从而防止产生精神活性作用。由于药物是半抗原，因此成功的疫苗依赖于适当的半抗原-蛋白载体缀合物的开发。然而，由于有效的疫苗需要诱导高水平和持久的抗体，并且由于滥用的 T 细胞非依赖性半抗原药物的注射不会诱导记忆回忆反应，因此在免疫接种过程中佐剂的作用至关重要。如本文所述，临床前研究通常使用强佐剂，如完全和不完全弗氏佐剂等，这些佐剂不能（或者在许多较新的佐剂的情况下，从未）在人类中使用。与此相反，在尼古丁和可卡因候选疫苗的人体临床试验中，唯一包含的佐剂是氢氧化铝凝胶。虽然铝盐已在世界范围内广泛用于许多许可疫苗，但人类对铝盐佐剂的半抗原药物免疫反应的经验表明，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、广泛可用、易于制造且具有成本效益的佐剂或佐剂组合。基于我们对该领域的回顾，我们建议以下佐剂组合用于研究或用于人类使用的产品开发：吸附于单磷酰脂质 A（MPLA）的铝盐；含有 MPLA 的脂质体[L（MPLA）]；吸附于铝盐的 L（MPLA）；水包油乳液；或含有 MPLA 的水包油乳液。
