Dataset Information


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.

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.

SUBMITTER: Robinson C 

PROVIDER: S-EPMC6605845 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC6361123 | BioStudies
2014-01-01 | S-EPMC4010527 | BioStudies
2014-01-01 | S-EPMC4018303 | BioStudies
| S-EPMC6598681 | BioStudies
2013-01-01 | S-EPMC3791856 | BioStudies
2013-01-01 | S-EPMC4120113 | BioStudies
2019-01-01 | S-EPMC7383364 | BioStudies
2018-01-01 | S-EPMC5949726 | BioStudies
2012-01-01 | S-EPMC3372705 | BioStudies
2020-01-01 | S-EPMC7142742 | BioStudies