Evaluation of Microparticulate (S)-4,5-Dihydroxy-2,3-pentanedione (DPD) as a Potential Vaccine Adjuvant

AAPS J. 2021 Jun 15;23(4):84. doi: 10.1208/s12248-021-00617-6.

Abstract

Adjuvants potentiate the immune response against co-inoculated antigens in the vaccine formulation. Based on the mechanism of action, the adjuvants are classified as immunostimulatory adjuvants and vaccine delivery systems. (S)-4,5-Dihydroxy-2,3-pentanedione (DPD) is the precursor of bacterial quorum sensing molecule, autoinducer (AI)-2. We tested the immunogenicity and adjuvant potential of microparticulate formulation of (S)-DPD via in vitro evaluation. By formulating the microparticles of (S)-DPD, we consolidated the advantages of both the classes of adjuvants. The microparticulate (S)-DPD was tested for its immunogenicity and cytotoxicity. We further tested its adjuvant effect by combining it with particulate vaccines for measles and gonorrhea and compared the adjuvant effect observed with the microparticulate formulations of the FDA-approved adjuvants alum, MPL A®, and MF59®. Microparticulate (S)-DPD was found to be non-cytotoxic towards the antigen-presenting cells and had an adjuvant effect with microparticulate gonorrhea vaccine. Further studies with additional bacterial vaccines and the in vivo evaluation will confirm the potential of microparticulate (S)-DPD as a probable vaccine adjuvant candidate.

Keywords: (S)-DPD; adjuvant; immunostimulatory; microparticle; quorum sensing.

MeSH terms

  • Adjuvants, Vaccine / administration & dosage*
  • Adjuvants, Vaccine / chemistry
  • Adjuvants, Vaccine / toxicity
  • Animals
  • Antigen Presentation / drug effects
  • Cell Line
  • Dendritic Cells
  • Drug Evaluation, Preclinical
  • Mice
  • Particle Size
  • Pentanes / administration & dosage
  • Pentanes / chemistry
  • Pentanes / immunology*
  • Pentanes / toxicity
  • Toxicity Tests, Acute

Substances

  • 4,5-dihydroxy-2,3-pentanedione
  • Adjuvants, Vaccine
  • Pentanes