title: Immunization to nicotine with a peptide-based vaccine composed of a conformationally biased agonist of C5a as a molecular adjuvant.
abstract: This paper describes the synthesis of a nicotine hapten (Nic) that possesses a carboxyl sidearm functional group allowing for conjugation to a peptide via amide bond formation. Nic was attached to the N-terminal amino group of a 19-residue peptide composed of a conformationally biased agonist of human C5a (YSFKPMPLaR), which is used as a molecular adjuvant and a B cell epitope of human MUC1 glycoprotein (YKQGGFLGL) to yield a peptide-based nicotine vaccine, NicYKQGGFLGLYSFKPMPLaR. Rats immunized with this vaccine were significantly less sensitive to behavioral effects (a Pavlovian discrimination task) induced by their exposure to high concentrations of nicotine (0.4 mg/kg) relative to their non-vaccinated counterparts. The attenuation of these nicotine-induced behavioral effects emanated from the presence of nicotine-specific antibodies (Abs) that were present in the sera of vaccinated rats even after their repeated exposure to high concentrations of nicotine during the time required to perform the behavioral assays. These results suggest that immunization with NicYKQGGFLGLYSFKPMPLaR in the absence of adjuvant is an effective means of inducing a nicotine-specific Ab response, which is capable of attenuating nicotine-induced behavioral/psychoactive effects.
authors.affiliation: School of Allied Health Professions, University of Nebraska Medical Center, 985155 Nebraska Medical Center, Omaha, NE 68198-5155, USA. sdsander@unmc.edu
authors.forename: Sam D
authors.initials: SD
authors.lastname: Sanderson
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Cheruku
authors.forename: Maniyan P
authors.initials: MP
authors.lastname: Padmanilayam
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Vennerstrom
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Thiele
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Palmatier
authors.forename: Rick A
authors.initials: RA
authors.lastname: Bevins
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001522:Behavior, Animal / Q000187:drug effects; D015936:Complement C5a / Q000819:agonists* / Q000276:immunology*; D008969:Molecular Sequence Data; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D022223:Vaccines, Subunit; D009538:Nicotine; D015936:Complement C5a