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

Christine Robinson, Carly Baehr, Shirdi E. Schmiel, Claudia Accetturo, Daniel L Mueller, Marco Pravetoni

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)909-917
Number of pages9
JournalHuman Vaccines and Immunotherapeutics
Volume15
Issue number4
DOIs
StatePublished - Apr 3 2019

Bibliographical note

Funding Information:
This work was supported by a Hennepin Healthcare Research Institute award (MP); NIH under Grant R01 DA041730 (MP); NIH under Grant T32DA007097 (CB); and the Socrates exchange program (CA).

Publisher Copyright:
© 2019, © 2019 Taylor & Francis Group, LLC.

Keywords

  • B cell
  • T cell
  • adjuvant
  • germinal center
  • opioid use disorder
  • oxycodone
  • vaccine

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