In the United States, opioid use disorders (OUD) and deadly overdoses constitute a national problem. Therapeutic vaccinations are a potential method for treating OUD and lowering the risk of overdose. In preclinical animals, immunisation with opioid-based haptens conjugated to immunogenic carriers induces opioid-specific antibodies that impede opioid distribution to the brain and decrease opioid-induced behaviour and toxicity. The purpose of this study was to see if the effectiveness of a lead oxycodone conjugate vaccine could be enhanced by using either aluminium hydroxide or the squalene-based oil-in-water emulsion MF59 adjuvant, which was recently FDA-approved for influenza vaccinations in individuals 65 and older. Alum formulation was more effective than MF59 in adult BALB/c mice at promoting the early development of hapten-specific B cells and the generation of oxycodone-specific serum IgG antibodies, as well as blocking oxycodone transport to the brain and oxycodone-induced motor activity. In adult C57Bl/6 mice vaccinated with a model peptide-protein combination, alum was more efficient than MF59 at inducing early differentiation of peptide-specific MHCII-restricted CD4+ Tfh and GC-Tfh cells. In contrast, in older C57Bl/6 mice, alum and MF59 were equally efficient in inducing hapten-specific B cells and peptide-specific MHCII-restricted CD4+ T cell development.

These findings show that alum is a more efficient adjuvant than MF59 in adult mice for combination vaccines targeting synthetic small molecule haptens or peptide antigens.