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

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-2,3pentanedione (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.

Subunit microparticulate vaccine delivery using microneedles trigger significant SARS-spike-specific humoral and cellular responses in a preclinical murine model

“…The cells were trypsinized and incubated with allophycocyanin-labeled and fluorescein isothiocyanate-labeled anti-mouse with the following pairs MHC-I, CD86 and MHC-II, CD40 according to manufacturer’s instructions (eBioscience laboratories, San Diego, CA), respectively for 1 h at 4 °C. Excess marker was washed with PBS before fluorescence intensity was measured using a BD Accuri C6 Plus flow cytometer (BD Bioscience, San Jose, CA) ( Joshi et al, 2021 ). Fig.…”

Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus

“…The percent recovery yield of the lyophilized product was calculated using the following formula [11,36].…”

“…Once administered, the vaccine antigen is recognized and engulfed by the circulating APCs via phagocytosis, which is then processed and presented on the surface of these cells via the MHC Class I or MHC class II pathways [34,37,40]. The expression of the antigen-presenting molecules, MHC I/II, and their co-stimulatory molecules, CD80/40, on the surface of DCs was assessed using fluorescent markers through flow cytometry analysis described previously [36][37][38]41]. For this purpose, murine DCs were plated in a 48-well plate at 3 x 10 4 cells/well density.…”

AI-2/Lux-S Quorum Sensing of Lactobacillus plantarum SS-128 Prolongs the Shelf Life of Shrimp (Litopenaeus vannamei): From Myofibril Simulation to Practical Application

“…Sam produces 4,5-dihydroxy-2,3-pentanedione (DPD) under the action of methyltransferase, adenosine homocysteine nucleosidase (PFS), and s-ribosylhomocysteine lyase (LuxS). DPD is the precursor of AI-2 [ 21 ]. The lactic acid bacteria count showed similar trends, indicating that the AI-2/LuxS QS in the L. plantarum ΔluxS could be offset by the existence of DPD.…”