Investigating Hapten Clustering as a Strategy to Enhance Vaccines against Drugs of Abuse

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.