title: Adjuvants for vaccines to drugs of abuse and addiction.
abstract: 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.
authors.affiliation: 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. Electronic address: calving@hivresearch.org.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.affiliation: 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.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matyas
authors.affiliation: 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; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Torres
authors.affiliation: 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; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.affiliation: 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; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Beck
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D004655:Emulsions / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology; D006241:Haptens / Q000276:immunology; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D008055:Lipids / Q000494:pharmacology; D008081:Liposomes / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000276:immunology / Q000628:therapy*; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D004655:Emulsions; D006241:Haptens; D008050:Lipid A; D008055:Lipids; D008081:Liposomes; D014612:Vaccines; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant; C048436:monophosphoryl lipid A
keywords: Adjuvants; Cocaine; Heroin; Hydrocodone; Immunotherapeutic vaccines; Methamphetamine; Morphine; Nicotine; Oxycodone
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