Novel liposomal formulations as adjuvant in transcutaneous vaccination: induction of chemokine and kytokine production in epitelial cells and improving protein passage through epidermis

IVANA REIDEL; GRIPPO, LUCÍA; BARTALINI LAURA; RUSSI ROMINA CECILIA; LECRON JC; MOREL F; GARCÍA, MARÍA INES; DIANA MARÍA MULLER; VEAUTE, CAROLINA; JÉGOU JF

Congreso; 5th European Congress of Immunology; 2018

Introduction: Liposomes are vaccine adjuvant systems able to transport hydro- and liposoluble molecules, allowing the co-incorporation of antigen and different immunostimulants. Our aim was to evaluate the adjuvanticity of a cationic liposomal formulation (Lip) with the addition of a CpG oligodeoxynucleotide (CpG-ODN) and/or an aminoacidic amphiphile (Gem) as immunostimulants, in the immunization against recombinant clumping factor of Staphylococcus aureus (rClf).Materials and Methods: Balb/c mice were immunized with: Lip+CpG-ODN+rClf, Lip+Gem+rClf, or Lip+Gem+CpG-ODN+rClf. Mice received three intradermal doses and were sacrificed three days after the last injection. Anti-rClf IgG was evaluated by indirect ELISA in plasma. Lymph nodes cells were analysed by flow cytometry to assess IL-4, IL-17 and IFN-γ production in CD4+ and CD8+ T cells. Results: Lip+CpG-ODN+rClf, Lip+Gem+rClf and Lip+Gem+CpG-ODN+rClf all led to high IgG levels. Formulations containing Gem or CpG-ODN increased the number of CD4+ lymphocytes. Lip+Gem+CpG-ODN+rClf significantly enhanced CD4+ cells compared to Lip+CpG-ODN+rClf. A similar trend was found for CD8+ lymphocytes. Gem and CpG-ODN were able to induce the production of IL-4 and IFN-γ by CD4+ cells and IFN-γ by CD8+ cells. Only Gem increased the production of IL-17 by CD4+ cells. Lip+Gem+CpG-ODN+rClf induced the highest number of CD4+ and CD8+ cells producing the three cytokines compared to Lip+CpG-ODN+rClf. Conclusions: Both Gem and CpG-ODN act as immunostimulants when introduced in liposomes, but their combination enhances the stimulant effect. It should be noted the cytotoxic cells stimulation by the Lip+Gem+CpG-ODN+rClf formulation, considering the impact of this profile in the design of viral or cancer preventive vaccines.