A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein

Vallecillo, María F. Sánchez; Escalera, María M. Minguito de la; Aguirre, Marina Laura; Gamboa, Gabriela Verónica Ullio; Palma, Santiago Daniel; González-Cintado, Leticia; Chiodetti, Ana L.; Soldano, Germán; Morón, Gabriel; Allemandi, Daniel Alberto; Ardavı́n, Carlos; Pistoresi-Palencia, María C.; Maletto, Belkys A.

doi:10.1016/j.jconrel.2015.07.008

Cited by 14 publications

(11 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14,15 Ascorbyl palmitate (AP), an amphiphilic derivative of ascorbic acid that has antioxidant activity, can also self-aggregate and form micellar structures in aqueous media. 16,17 Ascorbate has been shown to increase the effectiveness of various anticancer treatments. 18,19 Mixed micelles composed of TPGS and AP are nanosized colloidal particles with a hydrophobic core and a hydrophilic corona.…”

Section: Zhang Et Almentioning

confidence: 99%

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

Zhang¹,

Deyin²,

Che³

et al. 2017

IJN

View full text Add to dashboard Cite

Section: Zhang Et Almentioning

confidence: 99%

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

Zhang¹,

Deyin²,

Che³

et al. 2017

IJN

View full text Add to dashboard Cite

“…Although new adjuvants such as MF59 (ref. 59 ) and liquid crystals 60 are evolving, alum, as the oldest adjuvant, has shown certain new effects yet to be explored. Using alum as a nonspecific stimulus to modulate host immune responses in persistent infections is an interesting frontier for future study.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

Alum: an old dog with new tricks

Wen

Shi

2016

Emerging Microbes & Infections

View full text Add to dashboard Cite

Aluminum compounds (alum) are the most widely used adjuvants in veterinary and human vaccines. Alum was initially thought to be a simple depot for antigen retention; however, our understanding of the mechanism by which it works has progressed substantially in recent decades. Nonetheless, consensus regarding its roles in different aspects of immune regulation has not been reached, and it remains a long-standing research subject in the field of vaccinology. This review, in chronological order, discusses the various hypotheses proposed in mostly inadequate attempts to illuminate the mechanism by which alum works, from the depot theory to the involvement of the NLRP3 inflammasome and from cell death-associated danger factors to crystalline structure-mediated plasma membrane alteration. In addition, novel findings of unexpected beneficial effects of decreased HBV (Hepatitis B virus) viral load and HBeAg seroconversion in chronically infected patients, as well as significant tumor suppression in experimental mice following multiple alum-only injections are examined, revealing alum's potential clinical applications beyond its use as a simple tool in antigen preparation. With increasing threats of emerging microbes, originating from natural or man-made sources, that pose significant health concerns at the population scale, the potential use of alum as a ‘first-aid' vaccine is also discussed.

show abstract

“…Among other cytokines, IL-6 has been widely described as a promoter of the development of cytotoxic CD8 + T-cell ( 22 ) and antibody immunity in different adjuvant strategies ( 23 – 30 ). Since Coa-ASC16 enhances the CpG-ODN-induced humoral response ( 16 ) and that Coa-ASC16 alone (without antigen or CpG-ODN) is sensed by the innate immune system with a consequent local production of high amounts of IL-6 ( 31 ), we inquired whether this cytokine played a role in our model. To this end, we compared the antigen-specific immune response elicited by immunization with OVA/CpG-ODN/Coa-ASC16 in Il6 −/− vs. WT mice.…”

Section: Resultsmentioning

confidence: 99%

“…Based on their mechanisms of action, vaccine adjuvants are classified as immunostimulatory agents, depot systems or vehicles ( 2 , 4 ). In this regard, we have previously shown that Coa-ASC16 promotes antigen retention at the injection site (depot effect) and is sensed by the innate immune system promoting a transient local inflammatory environment involving the release of Damage-Associated Molecular Patterns, cytokines (IL-1β, IL-6, and IL-12) and recruitment of innate cells (neutrophils and Ly6C high monocytes) ( 31 ). These facts indicate Coa-ASC16 acts as an antigen reservoir and immunostimulatory agent.…”

Section: Discussionmentioning

confidence: 99%

Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen

et al. 2018

Self Cite

View full text Add to dashboard Cite

There is a need for new vaccine adjuvant strategies that offer both vigorous antibody and T-cell mediated protection to combat difficult intracellular pathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 or coagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previous results demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellular responses without toxic systemic effects. These responses were superior to those induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In this study, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicit CD8+ T-cell response and some of the underlying cellular and molecular mechanisms involved in adaptive response. We also analyzed whether this adjuvant strategy allows a switch from an immunization scheme of three-doses to one of single-dose. Our results demonstrated that vaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoral response and importantly-high quality CD8+ T-cell immunity with a single-dose immunization. Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells. The CD8+ T-cell response induced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferons and independent of CD4+ T-cells, and showed polyfunctionality and efficiency against an intracellular pathogen. Furthermore, the cellular and humoral responses elicited by the nanostructured formulation were IL-6-independent. This system provides a simple and inexpensive adjuvant strategy with great potential for future rationally designed vaccines.

show abstract

A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein

Cited by 14 publications

References 52 publications

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

Alum: an old dog with new tricks

Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen

Contact Info

Product

Resources

About

A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein

Cited by 14 publications

References 52 publications

Ascorbyl palmitate/d-&alpha;-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

Ascorbyl palmitate/d-&alpha;-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

Alum: an old dog with new tricks

Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen

Contact Info

Product

Resources

About

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo