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Alum adjuvant is more effective than MF59 at prompting early germinal center formation in response to peptide-protein conjugates and enhancing efficacy of a vaccine against opioid use disorders

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  • Alum adjuvant is more effective than MF59 at prompting early germinal center formation in response to peptide-protein conjugates and enhancing efficacy of a vaccine against opioid use disorders

    Hum Vaccin Immunother. 2019 Jan 9. doi: 10.1080/21645515.2018.1558697. [Epub ahead of print]
    Alum adjuvant is more effective than MF59 at prompting early germinal center formation in response to peptide-protein conjugates and enhancing efficacy of a vaccine against opioid use disorders.

    Robinson C1, Baehr C1,2, Schmiel SE3, Accetturo C4, Mueller DL5,6, Pravetoni M1,5,6,7.
    Author information

    Abstract

    Opioid use disorders (OUD) and fatal overdoses are a national emergency in the United States. Therapeutic vaccines offer a promising strategy to treat OUD and reduce the incidence of overdose. Immunization with opioid-based haptens conjugated to immunogenic carriers elicits opioid-specific antibodies that block opioid distribution to the brain and reduce opioid-induced behavior and toxicity in pre-clinical models. This study tested whether the efficacy of a lead oxycodone conjugate vaccine was improved by formulation in either aluminum hydroxide or the squalene-based oil-in-water emulsion MF59 adjuvant, which was recently FDA-approved for influenza vaccines in subjects 65+ years old. In adult BALB/c mice, alum formulation was more effective than MF59 at promoting the early expansion of hapten-specific B cells and the production of oxycodone-specific serum IgG antibodies, as well as blocking oxycodone distribution to the brain and oxycodone-induced motor activity. Alum was also more effective than MF59 at promoting early differentiation of peptide-specific MHCII-restricted CD4+ Tfh and GC-Tfh cells in adult C57Bl/6 mice immunized with a model peptide-protein conjugate. In contrast, alum and MF59 were equally effective in promoting hapten-specific B cells and peptide-specific MHCII-restricted CD4+ T cell differentiation in older C57Bl/6 mice. These data suggest that alum is a more effective adjuvant than MF59 for conjugate vaccines targeting synthetic small molecule haptens or peptide antigens in adult, but not aged, mice.


    KEYWORDS:

    B cell; Germinal center; T cell; adjuvant; opioid use disorder; oxycodone; vaccine

    PMID: 30625019 DOI: 10.1080/21645515.2018.1558697
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