Potential of DPD ((S)-4,5-dihydroxy-2,3-pentanedione) Analogs in Microparticulate Formulation as Vaccine Adjuvants

Abstract

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is involved in bacterial communication. DPD is the precursor of signal molecule autoinducer-2 (AI-2) and has high potential to be used as a vaccine adjuvant. Vaccine adjuvants are compounds that enhance the stability and immunogenicity of vaccine antigens, modulate efficacy, and increase the immune response to a particular antigen. Previously, the microparticulate form of (S)-DPD was found to have an adjuvant effect with the gonorrhea vaccine. In this study, we evaluated the immunogenicity and adjuvanticity of several synthetic analogs of the (S)-DPD molecule, including ent—DPD((R)-4,5-dihydroxy-2,3-pentanedione), n-butyl—DPD ((S)-1,2-dihydroxy-3,4-octanedione), isobutyl—DPD ((S)-1,2-dihydroxy-6-methyl-3,4-heptanedione), n-hexyl—DPD ((S)-1,2-dihydroxy-3,4-decanedione), and phenyl—DPD ((S)-3,4-dihydroxy-1-phenyl-1,2-butanedione), in microparticulate formulations. The microparticulate formulations of all analogs of (S)-DPD were found to be noncytotoxic toward dendritic cells. Among these analogs, ent—DPD, n-butyl—DPD, and isobutyl—DPD were found to be immunogenic toward antigens and showed adjuvant efficacy with microparticulate gonorrhea vaccines. It was observed that n-hexyl—DPD and phenyl—DPD did not show any adjuvant effect. This study shows that synthetic analogs of (S)-DPD molecules are capable of eliciting adjuvant effects with vaccines. A future in vivo evaluation will further confirm that these analogs are promising vaccine adjuvants.

Intranasal Immunization for Zika in a Pre-Clinical Model

“…The microparticulate Zika vaccine was formulated via a double emulsion method developed by our lab [ 18 , 21 , 36 ]. The emulsion was lyophilized, then the microparticles were characterized for recovery yield, particle size (nm), polydispersity index (PDI), number of particles/mL determined by the laser particle counter [ 18 ], and zeta potential (mV).…”

“…In vitro immunostimulatory potential was conducted using the Griess assay [ 18 , 30 , 36 ]. The release of nitric oxide (NO) was analyzed by quantitating the oxidation product, nitrite, via this assay [ 18 , 36 ].…”

“…In vitro immunostimulatory potential was conducted using the Griess assay [ 18 , 30 , 36 ]. The release of nitric oxide (NO) was analyzed by quantitating the oxidation product, nitrite, via this assay [ 18 , 36 ]. In this test, the release of NO by dendritic cells (DC 2.4) helps to determine if the vaccine microparticles are immunogenic.…”