title: Liposomes containing monophosphoryl lipid A: a potent adjuvant system for inducing antibodies to heroin hapten analogs.
abstract: In order to create an effective immunization approach for a potential vaccine to heroin, liposomes containing monophosphoryl lipid A [L(MPLA)] were tested as an adjuvant system to induce antibodies to heroin hapten analogs. Four synthetic haptens and two immunization strategies were employed. In the first strategy, a hydrophobic 23 amino acid immunogenic peptide derived from the membrane proximal external region of gp41 from HIV-1 envelope protein was embedded as a carrier in the outer surface of L(MPLA), to which was conjugated a 15 amino acid universal T cell epitope and a terminal heroin hapten analog. In the second strategy, tetanus toxoid (TT) carrier protein was decorated with haptens by conjugation, and the hapten-conjugated protein was mixed with L(MPLA). After immunization of mice, each of the immunization strategies was effective for induction of IgG anti-hapten antibodies. The first immunization strategy induced a mean end-point IgG titer against one of two haptens tested of approximately 12,800; however, no detectable antibodies were induced against the liposome-associated HIV-1 carrier peptide. In the second immunization strategy, depending on the hapten used for decorating the TT, end-point IgG titers ranged from 100,000 to 6,500,000. In this strategy, in which hapten was conjugated to the TT, end-point IgG titers of 400,000 to the TT carrier were observed with each conjugate. However, upon mixing unconjugated TT with L(MPLA), anti-TT titers of 6,500,000 were observed. We conclude that L(MPLA) serves as a potent adjuvant for inducing antibodies to candidate heroin haptens. However, antibodies to the carrier peptide or protein were partly or completed inhibited by the presence of conjugated hapten.
authors.affiliation: Laboratory of Adjuvant and Antigen Research, U.S. 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.forename: Alexander V
authors.initials: AV
authors.lastname: Mayorov
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Jacobson
authors.forename: Kejun
authors.initials: K
authors.lastname: Cheng
authors.forename: Malliga R
authors.initials: MR
authors.lastname: Iyer
authors.forename: Fuying
authors.initials: F
authors.lastname: Li
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Beck
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000917:Antibody Formation; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D003932:Heroin / Q000276:immunology*; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009293:Opioid-Related Disorders / Q000276:immunology / Q000517:prevention & control; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013745:Tetanus Toxoid / Q000737:chemistry / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D015700:HIV Envelope Protein gp41; D006241:Haptens; D008050:Lipid A; D008081:Liposomes; D010455:Peptides; D013745:Tetanus Toxoid; D014612:Vaccines; D003932:Heroin; C048436:monophosphoryl lipid A