title: Investigating hapten clustering as a strategy to enhance vaccines against drugs of abuse.
abstract: Vaccines for drugs of abuse have yet to achieve full clinical relevance, largely due to poor/inconsistent immune responses in patients. The use of multivalent scaffolding as a means to tailor drug-hapten density and clustering was examined in the context of drug-immune response modulation. A modular trivalent hapten containing a diglycine spacer, triAM1(Gly)2, was synthesized and shown to elicit anti-nicotine antibodies at equivalent affinity and concentration to the monovalent AM1 analog, despite in this instance having a lower effective hapten density. Augmenting this data, the corresponding monovalent hapten AM1(Gly)2 resulted in enhanced antibody affinity and concentration. Drug-hapten clustering represents a new vaccine paradigm, and, while examined only in the context of nicotine, it should be readily translatable to other drugs of abuse.
authors: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors: Karen C
authors: KC
authors: Collins
authors: Kim D
authors: KD
authors: Janda
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D013287:Illicit Drugs / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008968:Molecular Conformation; D009538:Nicotine / Q000032:analysis; D015813:Substance Abuse Detection; D014612:Vaccines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*
chemical_list: D006241:Haptens; D013287:Illicit Drugs; D014612:Vaccines; D009538:Nicotine