Alum adjuvant is more effective than MF59 in promoting early germinal center formation in response to peptide-protein conjugates and enhancing efficacy of candidate vaccines against opioid abuse in adult and old mice

Abstract

Abstract Heroin and prescription opioid abuse and overdose have been declared a national emergency in the United States. Compared to current medications, vaccines provide a complementary long-lasting, safe and cost-effective therapeutic strategy. Since the efficacy of vaccines against drugs of abuse is contingent upon achieving high antibody levels in immunized subjects, this study tested whether vaccines against oxycodone were more effective when formulated in the well-established aluminum hydroxide or the squalene-based oil-in-water emulsion MF59 adjuvant. Alum was more effective in inducing early expansion of hapten-specific germinal center (GC) B cells, and in inducing oxycodone-specific serum IgG antibodies that were effective in blocking oxycodone-induced motor activity in BALB/c adult mice. Alum was also more effective than MF59 in promoting early, but not late, differentiation of antigen-specific MHCII-restricted GC-Tfh cells in C57Bl/6 adult mice immunized with a model peptide-protein conjugate vaccine. Finally, alum and MF59 adjuvants displayed equivalent stimulation of hapten-specific B cells and peptide-specific T cells in old mice. Alum was significantly more effective, or at least equivalent to MF59 in eliciting protective responses against the highly-abused prescription opioid oxycodone and inducing early germinal center formation in response to hapten and peptide antigens in both adult and aging mice.