Stable assemblies of cationic bilayer fragments and CpG oligonucleotide with enhanced immunoadjuvant activity in vivo

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

“…Moreover, by conjugating CpG to NPs, we could use a low dose of CpG to potently activate DCs in the LNs without substantially raising blood levels of the inflammatory cytokines TNF-α, IL-12p70, and IL-6 (Fig. S2); thus, the low dose of CpG used on the NP appears to limit toxicity that would be associated with higher doses of free CpG (9,35). Vaccination with NP-CpG-B and NP-OVA increased the proportion of CD8 + T cells capable of degranulating and secreting IFN-γ compared with vaccination with soluble CpG-B and NP-OVA.…”

“…Induction of long-lasting CTLs with subunit vaccines requires, first, delivery of antigen to cross-presenting dendritic cells (DCs) and, second, potent activation of these DCs by the vaccine adjuvant, which instructs DCs how to activate T cells. Nanocarriers can be used to modulate the immune response induced by antigens and adjuvants by modifying their characteristics, such as stability, tissue and cell targeting, and DC-activating capacity (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). We have previously described the targeting benefits of conjugating antigens to ultrasmall Pluronic-stabilized poly(propylene sulfide) (PPS) nanoparticles (NPs) in terms of CD8 + T-cell and Th1 responses (13,14).…”

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

“…DNA has been extensively employed as a biotechnological tool, with applications in different forms of genetic modification, such as gene therapy and silencing (Fichou and Gersbach 2016), in vaccine development (Aps et al 2016) and as vaccine adjuvants (Rozenfeld et al 2012), and even in the delivery of macromolecules (as hydrogels and DNA cages) (Campolongo et al 2010;Walsh et al 2011). In many of these applications, the DNA molecules used are either in the form of long and circular plasmids (see, for example, Aps et al 2016;Robinson-Hamm and Gersbach 2016) or as small linear oligonucleotides (Fichou and Férec 2006;Rozenfeld et al 2012).…”

“…In many of these applications, the DNA molecules used are either in the form of long and circular plasmids (see, for example, Aps et al 2016;Robinson-Hamm and Gersbach 2016) or as small linear oligonucleotides (Fichou and Férec 2006;Rozenfeld et al 2012). The effect of small single-stranded DNA oligonucleotides on the structure of DODAB vesicles has been studied with ESR spectroscopy (Rozenfeld et al 2015a).…”

“…Versatile DODAB membranes have been used as nucleic acid (Silva et al 2011) and hydrophobic drug carriers Vieira et al 2006), as templates for polymerization and deposition of materials (Hubert et al 2000), as biomimetic particles (Rosa et al 2008), as microbicidal agents (Ragioto et al 2014) and as vaccine adjuvants (Rozenfeld et al 2012;Aps et al 2016). Similarly, highly fusogenic diC14-amidine membranes (Oliveira et al 2012) have successfully delivered nucleic acids (El Ouahabi et al 1996;Ruysschaert et al 1994) and stimulated the formation of immune responses (Tanaka et al 2008).…”