title: Enhanced immunogenicity of a bivalent nicotine vaccine.
abstract: The efficacy of nicotine vaccines for smoking cessation is dependent upon their ability to elicit sufficiently high serum antibody concentrations. This study compared two nicotine immunogens representing different hapten presentations, 3'-aminomethyl nicotine conjugated to recombinant Pseudomonas exoprotein A (3'-AmNic-rEPA) and 6-carboxymethlureido nicotine conjugated to keyhole limpet hemocyanin (6-CMUNic-KLH), and assessed whether their concurrent administration would produce additive serum antibody concentrations in rats. Effects of vaccination on nicotine pharmacokinetics were also studied. Vaccination of rats with these immunogens produced non cross-reacting nicotine-specific antibodies (NicAb). Serum NicAb concentrations elicited by each individual immunogen were not affected by whether the immunogens were administered alone as monovalent vaccines or together as a bivalent vaccine. The total NicAb concentration in the bivalent vaccine group was additive compared to that of the monovalent vaccines alone. Higher serum NicAb concentrations, irrespective of which immunogen elicited the antibodies, were associated with greater binding of nicotine in serum, a lower unbound nicotine concentration in serum, and lower brain nicotine concentration. These results demonstrate that it is possible to design immunogens which provide distinct nicotine epitopes for immune presentation, and which produce additive serum antibody levels. The concurrent administration of these immunogens as a bivalent vaccine may provide a general strategy for enhancing the antibody response to small molecules such as nicotine.
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN, United States.
authors.forename: D E
authors.initials: DE
authors.lastname: Keyler
authors.forename: S A
authors.initials: SA
authors.lastname: Roiko
authors.forename: C A
authors.initials: CA
authors.lastname: Earley
authors.forename: M P
authors.initials: MP
authors.lastname: Murtaugh
authors.forename: P R
authors.initials: PR
authors.lastname: Pentel
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D006433:Hemocyanins / Q000737:chemistry / Q000276:immunology*; D009538:Nicotine / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D012907:Smoking / Q000628:therapy*; D016540:Smoking Cessation / Q000379:methods*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018074:Vaccines, Conjugate; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D009538:Nicotine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin