title: Optimization of a methamphetamine conjugate vaccine for antibody production in mice.
abstract: There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants.
authors.affiliation: InterveXion Therapeutics, LLC, 4301 W. Markham St., #831, Little Rock, AR 72205, USA. Electronic address: misty.stevens@intervexion.com.
authors.forename: Misty W
authors.initials: MW
authors.lastname: Stevens
authors.affiliation: Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham St., #611, Little Rock, AR 72205, USA. Electronic address: mgunnell@uams.edu.
authors.forename: Melinda G
authors.initials: MG
authors.lastname: Gunnell
authors.affiliation: InterveXion Therapeutics, LLC, 4301 W. Markham St., #831, Little Rock, AR 72205, USA; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham St., #611, Little Rock, AR 72205, USA. Electronic address: r_tawney@hotmail.com.
authors.forename: Rachel
authors.initials: R
authors.lastname: Tawney
authors.affiliation: InterveXion Therapeutics, LLC, 4301 W. Markham St., #831, Little Rock, AR 72205, USA; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham St., #611, Little Rock, AR 72205, USA. Electronic address: mowens@uams.edu.
authors.forename: S Michael
authors.initials: SM
authors.lastname: Owens
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation; D005260:Female; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage*; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D005960:Glucosides; D008050:Lipid A; D018074:Vaccines, Conjugate; C000608161:glucopyranosyl lipid-A; D008694:Methamphetamine; D000536:Aluminum Hydroxide
keywords: Adjuvant; Drug abuse; Hapten density; Methamphetamine; Preclinical study; Therapeutic vaccine