Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

Abstract

Purpose To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. Methods OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. Results The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. Conclusion The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

Emerging skin-targeted drug delivery strategies to engineer immunity: A focus on infectious diseases

“…Numerous novel immunization strategies, including multicomponent (e.g., Figure 3) and temporal release vaccination, have been devised with MNAs to further improve the efficacy, longevity, breadth, and protection capacity of MNA- administered vaccines. To this end, several different immunestimulants/adjuvants, such as imiquimod (TLR7/8 agonist), c-di-GMP (STING pathway agonist), polyinosinic:polycytidylic acid (poly(I:C), a TLR3 agonist), platycodin (saponin adjuvant), monophosphoryl lipid A (TLR4 agonist), Quil-A (saponin adjuvant), resiquimod (TLR7/8 agonist), glucopyranosyl lipid adjuvant (GLA, TLR4 ligand), or CpG oligonucleotides (TLR9 ligand), have been used with the same MNAs to enhance the immune responses to the antigen delivered to the skin [214][215][216][217][218][219][220][221][222][223][224]. A few small-molecule adjuvants, such as imiquimod, could also be topically applied to the skin prior to MNA delivery of antigens or could be formulated with STAR particles and SNAs for enhanced topical vaccination.…”

Characterization of a novel thermostable and xylose-tolerant GH 39 β-xylosidase from Dictyoglomus thermophilum

“…Saponin is a kind of bioactive substance with a range of physiological functions, such as anti-inflammatory, anti-cancer, immunoregulatory and anti-fatigue effects [ 14 , 15 ]. Various saponins have disparate physiological activities as a result of diverse skeletons and sugar moieties.…”

Microarray patches enable the development of skin-targeted vaccines against COVID-19

“…To further improve the quality of MAP-based skin-targeted vaccination, several chemical and biological adjuvants (also known as immune-enhancers) have also been evaluated in pre-clinical studies [ 195 , 270 , 289 , 290 , 319 , 320 , 322 , [345] , [346] , [347] , [348] , [349] , [350] , [351] , [352] ]. For instance, one study investigated the effects of two different TLR agonists (imiquimod, a TLR7 agonist, and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist) on humoral and cell-mediated immune responses in mice immunized with coated MAPs loaded with influenza antigen [ 351 ].…”