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

Abstract

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.

A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production

“…Along with this, the antigen was formulated with a novel adjuvant strategy, CpG-ODN/Coa-ASC16, that constitutes a nanoplatform. This adjuvant strategy is able to induce potent Th1 and Th17 responses, and elicit long-term antibody responses (27,28). In this study we demonstrated that the immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 increases the survival against F. hepatica challenge.…”

“…In this line, the adjuvant capacity of the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) (agonist of TLR9) formulated with liquid crystal-type nanostructures formed by self-assembly from ascorbyl 6-Opalmitate ester (Coa-ASC16) has been demonstrated. The immunization of mice with the ovalbumin (OVA) protein, together with the adjuvant CpG-ODN/Coa-ASC16, induced a potent antigen-specific antibodies and Th1/Th17/CD8 + T-cell cellular responses without toxic systemic effects (27,28).…”

A natural oil increases specific anti-OVA IgG levels and induces a cellular immune response combined with aluminum hydroxide

“…The OVA-specific antibody titers were measured by ELISA as described by Chiodetti et al 18 Titer was considered to be the reciprocal of the last serum dilution that yielded an absorbance value 490 nm greater than that of twice the mean value of blank. The sera from nonimmunized mice were not reactive to OVA.…”

Development of a broadly active influenza intranasal vaccine adjuvanted with self-assembled particles composed of mastoparan-7 and CpG

“…CpG is an adjuvant composed of multiple synthetic oligodeoxynucleotides (rich in unmethylated cytosine-guanine motifs) with the capacity to induce expression of proinflammatory cytokines and costimulatory molecules in multiple cells, including dendritic cells (DCs), macrophages, and total leukocytes (31)(32)(33). CpG-adjuvanted vaccines generate long-lasting antibody responses as well as CD4 + and CD8 + T-cell responses against co-immunized antigens like OVA (34). Importantly, CpG promotes type-I interferon release and Th1 responses against different coadministered antigens, both of which are important in generating effective antiviral responses (35,36).…”