Frontiers in Immunology (Oct 2018)

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

  • Ana L. Chiodetti,
  • Ana L. Chiodetti,
  • María F. Sánchez Vallecillo,
  • María F. Sánchez Vallecillo,
  • Joseph S. Dolina,
  • María I. Crespo,
  • María I. Crespo,
  • Constanza Marin,
  • Constanza Marin,
  • Stephen P. Schoenberger,
  • Daniel A. Allemandi,
  • Daniel A. Allemandi,
  • Santiago D. Palma,
  • Santiago D. Palma,
  • María C. Pistoresi-Palencia,
  • María C. Pistoresi-Palencia,
  • Gabriel Morón,
  • Gabriel Morón,
  • Belkys A. Maletto,
  • Belkys A. Maletto

DOI
https://doi.org/10.3389/fimmu.2018.02319
Journal volume & issue
Vol. 9

Abstract

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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.

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